13-110503126-C-T

Position:

chr13-110503126-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001846.4(COL4A2):c.3883C>T(p.Arg1295Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,462 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000070 ( 1 hom. )

Consequence

COL4A2
NM_001846.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.89

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 (HGNC:):

COL4A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09700784).

BP6

Variant 13-110503126-C-T is Benign according to our data. Variant chr13-110503126-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 722398.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000617 (94/152316) while in subpopulation AFR AF= 0.00221 (92/41580). AF 95% confidence interval is 0.00185. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.3883C>T	p.Arg1295Trp	missense_variant	42/48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS1	NR_046583.1 linkuse as main transcript	n.187-198G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 linkuse as main transcript	c.3883C>T	p.Arg1295Trp	missense_variant	42/48	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000650225.1 linkuse as main transcript	n.1538C>T		non_coding_transcript_exon_variant	13/19
COL4A2-AS1	ENST00000417970.2 linkuse as main transcript	n.187-198G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000137

AC:

AN:

248470

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.00201

Gnomad4 AMR exome

AF:

0.0000674

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000617

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.000706

ESP6500AA

AF:

0.00135

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000182

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

COL4A2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Benign

0.097

Eigen_PC

Benign

-0.082

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.097

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.34

Sift

Uncertain

0.0060

Sift4G

Benign

0.062

Polyphen

1.0

Vest4

0.22

MVP

0.92

MPC

0.96

ClinPred

0.12

GERP RS

3.8

Varity_R

0.083

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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