rs9521781

Positions:

• chr13-110458676-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1433-95T>C		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.266-390A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1433-95T>C		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000617564.2	c.689-95T>C		intron_variant		6		ENSP00000481492.3
COL4A2-AS2	ENST00000458403.2	n.266-390A>G		intron_variant		2

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

Gnomad4 AFR exome AF: 0.640

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.573

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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.580

Alfa AF: 0.598 Hom.: 5171

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-1.0
CADD	Benign	1.1
DANN	Benign	0.20

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