rs3803228

Positions:

chr13-110482511-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001846.4(COL4A2):c.2759-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,612,576 control chromosomes in the GnomAD database, including 27,049 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2742 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24307 hom. )

Consequence

COL4A2
NM_001846.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001324

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.445

Variant links:

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]

COL4A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-110482511-T-C is Benign according to our data. Variant chr13-110482511-T-C is described in ClinVar as [Benign]. Clinvar id is 311152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110482511-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.2759-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
COL4A2	ENST00000360467.7 linkuse as main transcript	c.2759-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_001846.4	P1
COL4A2	ENST00000483683.2 linkuse as main transcript	n.389-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
COL4A2	ENST00000650225.1 linkuse as main transcript	n.414-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28532

AN:

152070

Hom.:

2743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.172

AC:

43032

AN:

249480

Hom.:

3850

AF XY:

0.173

AC XY:

23388

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.180

AC:

262650

AN:

1460388

Hom.:

24307

Cov.:

AF XY:

0.179

AC XY:

130293

AN XY:

726400

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.188

AC:

28541

AN:

152188

Hom.:

2742

Cov.:

AF XY:

0.186

AC XY:

13822

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.179

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.179

Hom.:

2423

Bravo

AF:

0.191

Asia WGS

AF:

0.198

AC:

691

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Porencephaly 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.5

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over