Variant 13-110209921-A-C 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.615+59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,550,788 control chromosomes in the GnomAD database, including 104,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12663 hom., cov: 32)

Exomes 𝑓: 0.36 ( 91660 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.934

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:

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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=-0.85).

BP6

Variant 13-110209921-A-C is Benign according to our data. Variant chr13-110209921-A-C is described in ClinVar as [Benign]. Clinvar id is 1272047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110209921-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6 linkuse as main transcript	c.615+59T>G		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2 linkuse as main transcript	c.615+59T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.615+59T>G		intron_variant		1	NM_001845.6	P1	P02462-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60740

AN:

151962

Hom.:

12633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.374

AC:

93290

AN:

249314

Hom.:

18442

AF XY:

0.365

AC XY:

49355

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.242

Gnomad SAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.357

AC:

499675

AN:

1398708

Hom.:

91660

Cov.:

AF XY:

0.355

AC XY:

248490

AN XY:

699872

show subpopulations

Gnomad4 AFR exome

AF:

0.509

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.354

GnomAD4 genome

AF:

0.400

AC:

60829

AN:

152080

Hom.:

12663

Cov.:

AF XY:

0.399

AC XY:

29669

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.493

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.369

Hom.:

1937

Bravo

AF:

0.409

Asia WGS

AF:

0.313

AC:

1087

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.4

DANN

Benign

0.61

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