rs41275104

Positions:

chr13-110242745-A-G

Variant summary

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

The NM_001845.6(COL4A1):c.85-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,613,186 control chromosomes in the GnomAD database, including 35,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4349 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31005 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Splicing: ADA: 0.00004950

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.830

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:

COL4A1 (HGNC:):

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=-0.92).

BP6

Variant 13-110242745-A-G is Benign according to our data. Variant chr13-110242745-A-G is described in ClinVar as [Benign]. Clinvar id is 258264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110242745-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 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.85-11T>C		intron_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2 linkuse as main transcript	c.85-11T>C		intron_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.85-11T>C		intron_variant		1	NM_001845.6	ENSP00000364979.4		P02462-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33781

AN:

152096

Hom.:

4343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.00864

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.178

AC:

44779

AN:

251298

Hom.:

4886

AF XY:

0.183

AC XY:

24840

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.0843

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.00762

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.199

AC:

290851

AN:

1460972

Hom.:

31005

Cov.:

AF XY:

0.201

AC XY:

145729

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.0917

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.00554

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.222

AC:

33827

AN:

152214

Hom.:

4349

Cov.:

AF XY:

0.215

AC XY:

16016

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.00886

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.206

Hom.:

721

Bravo

AF:

0.228

Asia WGS

AF:

0.117

AC:

411

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 14, 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, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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

-0.92

CADD

Benign

6.3

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.0060

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