Variant 13-110163326-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001845.6(COL4A1):c.4249+137G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 764,244 control chromosomes in the GnomAD database, including 5,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.088 ( 793 hom., cov: 33)

Exomes 𝑓: 0.11 ( 4318 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.311

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 13-110163326-C-G is Benign according to our data. Variant chr13-110163326-C-G is described in ClinVar as [Benign]. Clinvar id is 1231553.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 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.4249+137G>C		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.4249+137G>C		intron_variant		1	NM_001845.6	P1	P02462-1

Frequencies

GnomAD3 genomes

AF:

0.0883

AC:

13433

AN:

152144

Hom.:

794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0966

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.100

GnomAD4 exome

AF:

0.113

AC:

69083

AN:

611982

Hom.:

4318

AF XY:

0.115

AC XY:

37389

AN XY:

326444

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0758

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0326

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.0882

AC:

13426

AN:

152262

Hom.:

793

Cov.:

AF XY:

0.0867

AC XY:

6452

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.0906

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.0141

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0966

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.0993

Alfa

AF:

0.0350

Hom.:

Bravo

AF:

0.0841

Asia WGS

AF:

0.0650

AC:

225

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.0

DANN

Benign

0.53

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