rs7990009

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001846.4(COL4A2):c.-232C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 293,478 control chromosomes in the GnomAD database, including 14,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7473 hom., cov: 33)

Exomes 𝑓: 0.30 ( 6665 hom. )

Consequence

COL4A2
NM_001846.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.145

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:

COL4A1 (HGNC:2202): (collagen type IV alpha 1 chain) This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

COL4A1 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 13-110307341-C-G is Benign according to our data. Variant chr13-110307341-C-G is described in ClinVar as [Benign]. Clinvar id is 311090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.-232C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2	NM_001846.4 link	c.-232C>G	5_prime_UTR_variant	Exon 1 of 48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A1	NM_001845.6 link	c.-314G>C	upstream_gene_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2 link	c.-314G>C	upstream_gene_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467 link	c.-232C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 48	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000360467 link	c.-232C>G	5_prime_UTR_variant	Exon 1 of 48	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A1	ENST00000375820.10 link	c.-314G>C	upstream_gene_variant		1	NM_001845.6	ENSP00000364979.4	P02462-1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47078

AN:

151682

Hom.:

7450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.262

GnomAD4 exome

AF:

0.300

AC:

42513

AN:

141688

Hom.:

6665

Cov.:

AF XY:

0.301

AC XY:

21514

AN XY:

71366

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.311

AC:

47140

AN:

151790

Hom.:

7473

Cov.:

AF XY:

0.314

AC XY:

23299

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.292

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.205

Hom.:

511

Bravo

AF:

0.307

Asia WGS

AF:

0.298

AC:

1028

AN:

3446

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brain small vessel disease 1 with or without ocular anomalies

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Porencephalic cyst

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Porencephaly 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.6

DANN

Benign

0.63

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