rs3803237

Positions:

• chr13-110465321-G-A

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.1777-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,481,516 control chromosomes in the GnomAD database, including 26,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2964 hom., cov: 34)
  • Exomes 𝑓: 0.18 (23777 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.546

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=-0.93).
• BP6: Variant 13-110465321-G-A is Benign according to our data. Variant chr13-110465321-G-A is described in ClinVar as [Benign]. Clinvar id is 1272038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1777-84G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1777-84G>A		intron_variant		5	NM_001846.4	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28824 AN: 152064 Hom.: 2964 Cov.: 34

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.183 AC: 243648 AN: 1329334 Hom.: 23777 AF XY: 0.182 AC XY: 118867 AN XY: 654004

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.190 AC: 28846 AN: 152182 Hom.: 2964 Cov.: 34 AF XY: 0.184 AC XY: 13708 AN XY: 74406

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.215

Alfa AF: 0.197 Hom.: 6365

Bravo AF: 0.195

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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.69

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: rs3803237; hg19: chr13-111117668;