rs72657953

chr13-110465726-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.1978+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 1,005,098 control chromosomes in the GnomAD database, including 3,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (582 hom., cov: 34)
  • Exomes 𝑓: 0.081 (2953 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35

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=-0.89).
• BP6: Variant 13-110465726-C-T is Benign according to our data. Variant chr13-110465726-C-T is described in ClinVar as [Benign]. Clinvar id is 1246921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1978+120C>T		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1978+120C>T		intron_variant		5	NM_001846.4	P1

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12818 AN: 152178 Hom.: 582 Cov.: 34

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0987

GnomAD4 exome AF: 0.0807 AC: 68791 AN: 852802 Hom.: 2953 AF XY: 0.0812 AC XY: 34826 AN XY: 428986

Gnomad4 AFR exome AF: 0.0914

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0746

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.0645

Gnomad4 NFE exome AF: 0.0779

Gnomad4 OTH exome AF: 0.0905

GnomAD4 genome AF: 0.0842 AC: 12817 AN: 152296 Hom.: 582 Cov.: 34 AF XY: 0.0844 AC XY: 6284 AN XY: 74470

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0972

Alfa AF: 0.0809 Hom.: 55

Bravo AF: 0.0893

Asia WGS AF: 0.0910 AC: 317 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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.38
Dann	Benign	0.56

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: rs72657953; hg19: chr13-111118073;