13-110344847-A-G

Position:

• chr13-110344847-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001846.4(COL4A2):​c.100-12625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 152,222 control chromosomes in the GnomAD database, including 64,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (64883 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.100-12625A>G		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.100-12625A>G		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000650540.1	c.100-12625A>G		intron_variant				ENSP00000497878.1
COL4A2	ENST00000400163.7	c.100-12625A>G		intron_variant		5		ENSP00000383027.4
COL4A2	ENST00000649101.1	c.100-12625A>G		intron_variant				ENSP00000497869.1

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139464 AN: 152104 Hom.: 64870 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.969

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.938

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.917 AC: 139528 AN: 152222 Hom.: 64883 Cov.: 32 AF XY: 0.919 AC XY: 68405 AN XY: 74422

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.969

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.969

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.990

Gnomad4 OTH AF: 0.937

Alfa AF: 0.940 Hom.: 10007

Bravo AF: 0.908

Asia WGS AF: 0.938 AC: 3262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.5
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4773161; hg19: chr13-110997194;