Variant rs1975514 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_001845.6(COL4A1):c.2969-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,596,810 control chromosomes in the GnomAD database, including 104,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.34 ( 8872 hom., cov: 32)

Exomes 𝑓: 0.36 ( 95984 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.279

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-110176544-T-C is Benign according to our data. Variant chr13-110176544-T-C is described in ClinVar as [Benign]. Clinvar id is 1293324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110176544-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 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.2969-31A>G		intron_variant		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.2969-31A>G		intron_variant		1	NM_001845.6	ENSP00000364979.4		P02462-1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51665

AN:

151916

Hom.:

8859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.356

AC:

89231

AN:

250612

Hom.:

16238

AF XY:

0.357

AC XY:

48372

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.302

Gnomad SAS exome

AF:

0.368

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.362

AC:

523171

AN:

1444776

Hom.:

95984

Cov.:

AF XY:

0.362

AC XY:

260885

AN XY:

719874

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.340

AC:

51718

AN:

152034

Hom.:

8872

Cov.:

AF XY:

0.340

AC XY:

25290

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.302

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.281

Hom.:

1548

Bravo

AF:

0.338

Asia WGS

AF:

0.362

AC:

1256

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.61

DANN

Benign

0.43

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

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