rs1556122

Positions:

• chr13-110333260-C-T

Variant summary

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

The NM_001846.4(COL4A2):​c.100-24212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,126 control chromosomes in the GnomAD database, including 31,212 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 0.63 (31212 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.100-24212C>T		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.100-24212C>T		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000400163.7	c.100-24212C>T		intron_variant		5		ENSP00000383027
COL4A2	ENST00000649101.1	c.100-24212C>T		intron_variant				ENSP00000497869
COL4A2	ENST00000650540.1	c.100-24212C>T		intron_variant				ENSP00000497878

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95829 AN: 152008 Hom.: 31195 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.630 AC: 95899 AN: 152126 Hom.: 31212 Cov.: 33 AF XY: 0.636 AC XY: 47276 AN XY: 74362

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.625

Alfa AF: 0.669 Hom.: 47017

Bravo AF: 0.619

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.42

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: rs1556122; hg19: chr13-110985607;