rs9515230

Positions:

• chr13-110469500-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.2203+176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,276 control chromosomes in the GnomAD database, including 636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.083 (636 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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 13-110469500-T-C is Benign according to our data. Variant chr13-110469500-T-C is described in ClinVar as [Benign]. Clinvar id is 1277784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2203+176T>C		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2203+176T>C		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000494852.2	c.123+176T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12710 AN: 152158 Hom.: 638 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0834 AC: 12705 AN: 152276 Hom.: 636 Cov.: 33 AF XY: 0.0832 AC XY: 6194 AN XY: 74454

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.104

Alfa AF: 0.106 Hom.: 886

Bravo AF: 0.0862

Asia WGS AF: 0.0990 AC: 344 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	-0.91
CADD	Benign	0.24
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9515230; hg19: chr13-111121847; COSMIC: COSV64628677;