rs72657977

Positions:

• chr13-110480066-C-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.2588-154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,256 control chromosomes in the GnomAD database, including 1,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1221 hom., cov: 34)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.72

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=-1.0).
• BP6: Variant 13-110480066-C-T is Benign according to our data. Variant chr13-110480066-C-T is described in ClinVar as [Benign]. Clinvar id is 1293754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2588-154C>T		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2588-154C>T		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000483683.2	n.218-154C>T		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000650225.1	n.243-154C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18440 AN: 152138 Hom.: 1221 Cov.: 34

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18450 AN: 152256 Hom.: 1221 Cov.: 34 AF XY: 0.118 AC XY: 8793 AN XY: 74442

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.130

Alfa AF: 0.132 Hom.: 172

Bravo AF: 0.122

Asia WGS AF: 0.0480 AC: 167 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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.54

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: rs72657977; hg19: chr13-111132413;