rs76536922

Positions:

• chr13-110307817-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.-44-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,489,710 control chromosomes in the GnomAD database, including 3,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (244 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2816 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.359

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-110307817-C-T is Benign according to our data. Variant chr13-110307817-C-T is described in ClinVar as [Benign]. Clinvar id is 1226919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.-44-43C>T		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.-44-43C>T		intron_variant		5	NM_001846.4	P1

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7816 AN: 152148 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0493

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0631

GnomAD4 exome AF: 0.0623 AC: 83361 AN: 1337444 Hom.: 2816 Cov.: 27 AF XY: 0.0624 AC XY: 40808 AN XY: 653870

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.0303

Gnomad4 SAS exome AF: 0.0557

Gnomad4 FIN exome AF: 0.0548

Gnomad4 NFE exome AF: 0.0662

Gnomad4 OTH exome AF: 0.0583

GnomAD4 genome AF: 0.0513 AC: 7817 AN: 152266 Hom.: 244 Cov.: 32 AF XY: 0.0514 AC XY: 3826 AN XY: 74452

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0757

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0538 Hom.: 36

Bravo AF: 0.0485

Asia WGS AF: 0.0420 AC: 147 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76536922; hg19: chr13-110960164;