rs7984937

chr13-110438562-T-C

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.862-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,607,394 control chromosomes in the GnomAD database, including 75,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10398 hom., cov: 33)
  • Exomes 𝑓: 0.29 (64642 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.148

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110438562-T-C is Benign according to our data. Variant chr13-110438562-T-C is described in ClinVar as [Benign]. Clinvar id is 1272751.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110438562-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.862-56T>C		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.862-56T>C		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000617564.2	c.119-56T>C		intron_variant
COL4A2	ENST00000650540.1	c.862-56T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53397 AN: 151780 Hom.: 10391 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.353

GnomAD3 exomes AF: 0.284 AC: 70880 AN: 249408 Hom.: 11379 AF XY: 0.282 AC XY: 38094 AN XY: 135322

Gnomad AFR exome AF: 0.543

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.222

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.290 AC: 422437 AN: 1455496 Hom.: 64642 Cov.: 30 AF XY: 0.288 AC XY: 208927 AN XY: 724546

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.352 AC: 53440 AN: 151898 Hom.: 10398 Cov.: 33 AF XY: 0.346 AC XY: 25709 AN XY: 74238

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.354

Alfa AF: 0.321 Hom.: 2360

Bravo AF: 0.364

Asia WGS AF: 0.211 AC: 733 AN: 3476

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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.3
Dann	Benign	0.27

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: rs7984937; hg19: chr13-111090909; COSMIC: COSV64631986;