Variant rs7990009 details in Genebe, Genetics Data Aggregator

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 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

Scores

Clinical Significance

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

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:

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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	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.-232C>G		5_prime_UTR_variant	1/48	ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7 linkuse as main transcript	c.-232C>G		5_prime_UTR_variant	1/48	5	NM_001846.4	P1

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brain small vessel disease 1 with or without ocular anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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. -

Porencephalic cyst

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

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