rs9515203

chr13-110397276-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.181-27458T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,192 control chromosomes in the GnomAD database, including 5,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5336 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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=-0.87).
• BP6: Variant 13-110397276-T-C is Benign according to our data. Variant chr13-110397276-T-C is described in ClinVar as [Benign]. Clinvar id is 1164920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.181-27458T>C		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.181-27458T>C		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000400163.7	c.181-27458T>C		intron_variant		5
COL4A2	ENST00000650540.1	c.181-27458T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39286 AN: 152074 Hom.: 5337 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39295 AN: 152192 Hom.: 5336 Cov.: 33 AF XY: 0.256 AC XY: 19036 AN XY: 74394

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.233

Alfa AF: 0.249 Hom.: 5233

Bravo AF: 0.266

Asia WGS AF: 0.145 AC: 506 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 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.98
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: rs9515203; hg19: chr13-111049623;