rs4773199

Positions:

Variant summary

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

The NM_001846.4(COL4A2):c.4089G>A(p.Ala1363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,587,136 control chromosomes in the GnomAD database, including 39,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4258 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34755 hom. )

Consequence

COL4A2
NM_001846.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.423

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-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

COL4A2-AS1 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=-0.74).

BP6

Variant 13-110503432-G-A is Benign according to our data. Variant chr13-110503432-G-A is described in ClinVar as [Benign]. Clinvar id is 311171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110503432-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.423 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.4089G>A	p.Ala1363=	synonymous_variant	43/48	ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1 linkuse as main transcript	n.187-504C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
COL4A2	ENST00000360467.7 linkuse as main transcript	c.4089G>A	p.Ala1363=	synonymous_variant	43/48	5	NM_001846.4	ENSP00000353654	P1
COL4A2-AS1	ENST00000417970.2 linkuse as main transcript	n.187-504C>T		intron_variant, non_coding_transcript_variant		3
COL4A2	ENST00000650225.1 linkuse as main transcript	n.1744G>A		non_coding_transcript_exon_variant	14/19

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34564

AN:

152024

Hom.:

4257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0442

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.196

AC:

40201

AN:

204648

Hom.:

4395

AF XY:

0.200

AC XY:

22191

AN XY:

110758

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.0538

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.215

AC:

307913

AN:

1434994

Hom.:

34755

Cov.:

AF XY:

0.215

AC XY:

152911

AN XY:

711708

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.0338

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.227

AC:

34572

AN:

152142

Hom.:

4258

Cov.:

AF XY:

0.220

AC XY:

16350

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.0439

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.230

Hom.:

2146

Bravo

AF:

0.233

Asia WGS

AF:

0.158

AC:

550

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	-	- -

Porencephaly 2

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.55

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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