rs56676181

chr13-110449584-C-T

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.1079-95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,203,346 control chromosomes in the GnomAD database, including 69,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7101 hom., cov: 33)
  • Exomes 𝑓: 0.34 (62411 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.243

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=-0.9).
• BP6: Variant 13-110449584-C-T is Benign according to our data. Variant chr13-110449584-C-T is described in ClinVar as [Benign]. Clinvar id is 1258504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1079-95C>T		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1079-95C>T		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000617564.2	c.336-95C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43354 AN: 152048 Hom.: 7096 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.340 AC: 357197 AN: 1051180 Hom.: 62411 AF XY: 0.342 AC XY: 177752 AN XY: 520458

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.404

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.285 AC: 43361 AN: 152166 Hom.: 7101 Cov.: 33 AF XY: 0.285 AC XY: 21235 AN XY: 74386

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.261

Alfa AF: 0.326 Hom.: 2015

Bravo AF: 0.259

Asia WGS AF: 0.277 AC: 966 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	-0.90
Cadd	Benign	0.85
Dann	Benign	0.63

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: rs56676181; hg19: chr13-111101931; COSMIC: COSV64636529;