rs3803232

Positions:

• chr13-110466949-A-G

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.2039-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,537,950 control chromosomes in the GnomAD database, including 264,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27910 hom., cov: 32)
  • Exomes 𝑓: 0.58 (236628 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.625

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110466949-A-G is Benign according to our data. Variant chr13-110466949-A-G is described in ClinVar as [Benign]. Clinvar id is 1238254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2039-91A>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2039-91A>G		intron_variant		5	NM_001846.4	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90525 AN: 151982 Hom.: 27874 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.578 AC: 800760 AN: 1385850 Hom.: 236628 AF XY: 0.575 AC XY: 396269 AN XY: 688736

Gnomad4 AFR exome AF: 0.722

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.596 AC: 90622 AN: 152100 Hom.: 27910 Cov.: 32 AF XY: 0.583 AC XY: 43363 AN XY: 74360

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.598

Alfa AF: 0.601 Hom.: 34254

Bravo AF: 0.605

Asia WGS AF: 0.402 AC: 1400 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	-0.91
CADD	Benign	1.2
DANN	Benign	0.35

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: rs3803232; hg19: chr13-111119296;