Variant-Normalization

Variant Normalization

The normalization of a variant representation in VCF consists of two parts: parsimony and left alignment pertaining to the nature of a variant's length and position respectively.

• Parsimony means representing a variant in as few nucleotides as possible without reducing the length of any allele to 0.

• Left aligning a variant means shifting the start position of that variant to the left till it is no longer possible to do so.

• A variant is normalized if and only if it is parsimonious and left-aligned

National Center for Clinical Laboratories(NCCL) 3'rule

所有变异都应按照靠近基因转录方向末端（3’ 端）的位置来表述（3’rule）

正链基因（以正链为模板转录，出现在重复序列上的突变根据转录本上的 3’rule 发生在 3’ 端，在基因组层面，也按照转录本上 3’ 端书写，即突变发生在重复序列的右侧）

负链基因（以负链为模板转录，出现在重复序列上的突变根据转录本上的 3’rule，发生在 3’ 端，在基因组层面，也按照转录本上 3’ 端书写，即突变发生在重复序列的左侧）

Example of Deletion variant normalization

Raw variant :

Chr	Pos	Ref	Alt	Gene	Strand	Type	Transcript
3	10183820	CCCTA	C	VHL	+	Deletion	NM_000551.4

Equivalent deletions :

Variant Normalization result :

Chr	Pos	Ref	Alt	Gene	Strand	Type	Transcript
3	10183823	TACC	-	VHL	+	Deletion	NM_000551.4

Example of Insertion variant normalization

Raw variant :

Chr	Pos	Ref	Alt	Gene	Strand	Type	Transcript
X	48649699	C	CTACT	GATA1	+	Insertion	NM_002049.4

Equivalent insertions :

Variant Normalization result:

Chr	Pos	Ref	Alt	Gene	Strand	Type	Transcript
X	48649703	-	TACT	GATA1	+	Insertion	NM_002049.4