rs9301460

chr13-110503806-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.4139-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,609,432 control chromosomes in the GnomAD database, including 110,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11531 hom., cov: 32)
  • Exomes 𝑓: 0.36 (98822 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-110503806-G-A is Benign according to our data. Variant chr13-110503806-G-A is described in ClinVar as [Benign]. Clinvar id is 1281130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.4139-41G>A		intron_variant		ENST00000360467.7
COL4A2-AS1	NR_046583.1	n.187-878C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.4139-41G>A		intron_variant		5	NM_001846.4	P1
COL4A2-AS1	ENST00000417970.2	n.187-878C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58431 AN: 151852 Hom.: 11520 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.376

GnomAD3 exomes AF: 0.348 AC: 86375 AN: 248350 Hom.: 15919 AF XY: 0.354 AC XY: 47738 AN XY: 134862

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.201

Gnomad SAS exome AF: 0.378

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.364 AC: 529898 AN: 1457462 Hom.: 98822 Cov.: 34 AF XY: 0.365 AC XY: 264575 AN XY: 725280

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.385 AC: 58471 AN: 151970 Hom.: 11531 Cov.: 32 AF XY: 0.384 AC XY: 28534 AN XY: 74290

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.373

Alfa AF: 0.382 Hom.: 2517

Bravo AF: 0.375

Asia WGS AF: 0.296 AC: 1031 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

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.8
Dann	Benign	0.55

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: rs9301460; hg19: chr13-111156153; COSMIC: COSV64632958; COSMIC: COSV64632958;