rs9521781

Variant names:

• chr13-110458676-T-C
• rs9521781
• NM_001846.4:c.1433-95T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.1433-95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,474,248 control chromosomes in the GnomAD database, including 248,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25460 hom., cov: 31)
  • Exomes 𝑓: 0.57 (223439 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27
• Publications: 5 publications found

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]

COL4A2-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 13-110458676-T-C is Benign according to our data. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458676-T-C is described in CliVar as Benign. Clinvar id is 1260839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1433-95T>C		intron_variant	Intron 21 of 47	ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.266-390A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1433-95T>C		intron_variant	Intron 21 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86471 AN: 151436 Hom.: 25434 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.573 AC: 758108 AN: 1322694 Hom.: 223439 AF XY: 0.571 AC XY: 377312 AN XY: 660524

African (AFR) AF: 0.640 AC: 19153 AN: 29944

American (AMR) AF: 0.389 AC: 15060 AN: 38730

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 14519 AN: 21970

East Asian (EAS) AF: 0.183 AC: 7110 AN: 38900

South Asian (SAS) AF: 0.474 AC: 35997 AN: 76000

European-Finnish (FIN) AF: 0.445 AC: 22056 AN: 49608

Middle Eastern (MID) AF: 0.677 AC: 3561 AN: 5258

European-Non Finnish (NFE) AF: 0.605 AC: 609053 AN: 1007122

Other (OTH) AF: 0.573 AC: 31599 AN: 55162

GnomAD4 genome AF: 0.571 AC: 86548 AN: 151554 Hom.: 25460 Cov.: 31 AF XY: 0.558 AC XY: 41342 AN XY: 74062

African (AFR) AF: 0.631 AC: 26049 AN: 41274

American (AMR) AF: 0.488 AC: 7443 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2355 AN: 3466

East Asian (EAS) AF: 0.225 AC: 1157 AN: 5152

South Asian (SAS) AF: 0.458 AC: 2204 AN: 4812

European-Finnish (FIN) AF: 0.427 AC: 4488 AN: 10522

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40810 AN: 67792

Other (OTH) AF: 0.580 AC: 1221 AN: 2104

Alfa AF: 0.599 Hom.: 5310

Bravo AF: 0.578

Asia WGS AF: 0.372 AC: 1297 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.20
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9521781; hg19: chr13-111111023; COSMIC: COSV64632000; COSMIC: COSV64632000;