rs7990214

Positions:

chr13-110458826-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001846.4(COL4A2):c.1488G>A(p.Pro496=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,380 control chromosomes in the GnomAD database, including 273,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25717 hom., cov: 31)

Exomes 𝑓: 0.58 ( 248200 hom. )

Consequence

COL4A2
NM_001846.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.28

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:

COL4A2-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

COL4A2-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 13-110458826-G-A is Benign according to our data. Variant chr13-110458826-G-A is described in ClinVar as [Benign]. Clinvar id is 311128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458826-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 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.1488G>A	p.Pro496=	synonymous_variant	22/48	ENST00000360467.7
COL4A2-AS2	NR_171022.1 linkuse as main transcript	n.266-540C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COL4A2	ENST00000360467.7 linkuse as main transcript	c.1488G>A	p.Pro496=	synonymous_variant	22/48	5	NM_001846.4	P1
COL4A2-AS2	ENST00000458403.2 linkuse as main transcript	n.266-540C>T		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000617564.2 linkuse as main transcript	c.747G>A	p.Pro249=	synonymous_variant	10/10

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86933

AN:

151882

Hom.:

25692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.676

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.579

GnomAD3 exomes

AF:

0.521

AC:

129568

AN:

248926

Hom.:

35770

AF XY:

0.525

AC XY:

70948

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.575

AC:

840890

AN:

1461380

Hom.:

248200

Cov.:

AF XY:

0.574

AC XY:

416948

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.644

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.606

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

AF:

0.572

AC:

87008

AN:

152000

Hom.:

25717

Cov.:

AF XY:

0.560

AC XY:

41594

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.225

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.598

Hom.:

19062

Bravo

AF:

0.579

Asia WGS

AF:

0.372

AC:

1296

AN:

3478

EpiCase

AF:

0.607

EpiControl

AF:

0.609

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

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

Porencephaly 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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

-0.78

CADD

Benign

0.095

DANN

Benign

0.83

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

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