rs7992330

chr13-110462404-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):c.1776+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,609,344 control chromosomes in the GnomAD database, including 62,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4444 hom., cov: 33)
  • Exomes 𝑓: 0.28 (58437 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302

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]

COL4A2-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-110462404-G-A is Benign according to our data. Variant chr13-110462404-G-A is described in ClinVar as [Benign]. Clinvar id is 1165077.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110462404-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1776+20G>A		intron_variant		ENST00000360467.7
COL4A2-AS2	NR_171022.1	n.265+619C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1776+20G>A		intron_variant		5	NM_001846.4	P1
COL4A2-AS2	ENST00000458403.2	n.265+619C>T		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000478681.1	n.292G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34659 AN: 152090 Hom.: 4444 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.231 AC: 56185 AN: 242810 Hom.: 7176 AF XY: 0.238 AC XY: 31651 AN XY: 132770

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.0880

Gnomad SAS exome AF: 0.249

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.277 AC: 403539 AN: 1457136 Hom.: 58437 Cov.: 32 AF XY: 0.277 AC XY: 200672 AN XY: 724980

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0878

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.228 AC: 34661 AN: 152208 Hom.: 4444 Cov.: 33 AF XY: 0.224 AC XY: 16651 AN XY: 74426

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0964

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.209

Alfa AF: 0.264 Hom.: 1055

Bravo AF: 0.215

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.23
Dann	Benign	0.71

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: rs7992330; hg19: chr13-111114751; COSMIC: COSV64636707; COSMIC: COSV64636707;