rs4773194

Positions:

• chr13-110480143-A-G
• chr13-110480143-A-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.2588-77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,423,328 control chromosomes in the GnomAD database, including 476,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (50726 hom., cov: 34)
  • Exomes 𝑓: 0.82 (425950 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.257

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=-0.99).
• BP6: Variant 13-110480143-A-G is Benign according to our data. Variant chr13-110480143-A-G is described in ClinVar as [Benign]. Clinvar id is 1227135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2588-77A>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2588-77A>G		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000483683.2	n.218-77A>G		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000650225.1	n.243-77A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124095 AN: 152134 Hom.: 50674 Cov.: 34

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.834

GnomAD4 exome AF: 0.818 AC: 1039608 AN: 1271076 Hom.: 425950 AF XY: 0.820 AC XY: 514424 AN XY: 627224

Gnomad4 AFR exome AF: 0.778

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.871

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.871

Gnomad4 FIN exome AF: 0.847

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.826

GnomAD4 genome AF: 0.816 AC: 124208 AN: 152252 Hom.: 50726 Cov.: 34 AF XY: 0.818 AC XY: 60919 AN XY: 74448

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.837

Alfa AF: 0.817 Hom.: 28268

Bravo AF: 0.811

Asia WGS AF: 0.861 AC: 2996 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	-0.99
CADD	Benign	0.23
DANN	Benign	0.40

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: rs4773194; hg19: chr13-111132490; COSMIC: COSV64626218;