rs61749897

Positions:

chr13-110186467-A-G

Variant summary

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

The NM_001845.6(COL4A1):c.1815T>C(p.Pro605=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 1,613,636 control chromosomes in the GnomAD database, including 4,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 455 hom., cov: 33)

Exomes 𝑓: 0.074 ( 4539 hom. )

Consequence

COL4A1
NM_001845.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.738

Variant links:

Genes affected

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 13-110186467-A-G is Benign according to our data. Variant chr13-110186467-A-G is described in ClinVar as [Benign]. Clinvar id is 195950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110186467-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.738 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6 linkuse as main transcript	c.1815T>C	p.Pro605=	synonymous_variant	26/52	ENST00000375820.10	NP_001836.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.1815T>C	p.Pro605=	synonymous_variant	26/52	1	NM_001845.6	ENSP00000364979	P1	P02462-1
COL4A1	ENST00000649738.1 linkuse as main transcript	n.1945T>C		non_coding_transcript_exon_variant	26/31

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11932

AN:

152144

Hom.:

455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0826

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0692

Gnomad FIN

AF:

0.0913

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0736

GnomAD3 exomes

AF:

0.0827

AC:

20623

AN:

249444

Hom.:

1007

AF XY:

0.0793

AC XY:

10728

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.0898

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.0697

Gnomad FIN exome

AF:

0.0894

Gnomad NFE exome

AF:

0.0690

Gnomad OTH exome

AF:

0.0647

GnomAD4 exome

AF:

0.0745

AC:

108857

AN:

1461374

Hom.:

4539

Cov.:

AF XY:

0.0738

AC XY:

53657

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.0883

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.0690

Gnomad4 FIN exome

AF:

0.0875

Gnomad4 NFE exome

AF:

0.0711

Gnomad4 OTH exome

AF:

0.0673

GnomAD4 genome

AF:

0.0784

AC:

11943

AN:

152262

Hom.:

455

Cov.:

AF XY:

0.0800

AC XY:

5952

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0872

Gnomad4 AMR

AF:

0.0826

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.0692

Gnomad4 FIN

AF:

0.0913

Gnomad4 NFE

AF:

0.0702

Gnomad4 OTH

AF:

0.0738

Alfa

AF:

0.0664

Hom.:

142

Bravo

AF:

0.0805

Asia WGS

AF:

0.103

AC:

357

AN:

3478

EpiCase

AF:

0.0630

EpiControl

AF:

0.0630

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2017	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	clinical testing	Athena Diagnostics	Jun 02, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 14, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

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

Brain small vessel disease 1 with or without ocular anomalies

Benign:1

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. -

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

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

DANN

Benign

0.32

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