rs378601

Positions:

• chr13-110501587-G-A
• chr13-110501587-G-C
• chr13-110501587-G-T

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.3761-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,217,880 control chromosomes in the GnomAD database, including 597,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70055 hom., cov: 33)
  • Exomes 𝑓: 0.99 (527491 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

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=-0.85).
• BP6: Variant 13-110501587-G-A is Benign according to our data. Variant chr13-110501587-G-A is described in ClinVar as [Benign]. Clinvar id is 1239667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.3761-81G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.3761-81G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000650225.1	n.1416-81G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145656 AN: 152180 Hom.: 70010 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.973

GnomAD4 exome AF: 0.995 AC: 1059905 AN: 1065582 Hom.: 527491 AF XY: 0.995 AC XY: 545385 AN XY: 547884

Gnomad4 AFR exome AF: 0.835

Gnomad4 AMR exome AF: 0.992

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.988

GnomAD4 genome AF: 0.957 AC: 145759 AN: 152298 Hom.: 70055 Cov.: 33 AF XY: 0.959 AC XY: 71381 AN XY: 74458

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.974

Alfa AF: 0.971 Hom.: 9293

Bravo AF: 0.951

Asia WGS AF: 0.990 AC: 3443 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	-0.85
CADD	Benign	1.2
DANN	Benign	0.60

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: rs378601; hg19: chr13-111153934;