Variant 13-110164824-G-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.4150+38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,607,758 control chromosomes in the GnomAD database, including 116,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9840 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106583 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.33

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=-0.91).

BP6

Variant 13-110164824-G-C is Benign according to our data. Variant chr13-110164824-G-C is described in ClinVar as [Benign]. Clinvar id is 1217362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110164824-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 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.4150+38C>G		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.4150+38C>G	intron_variant	1	NM_001845.6	P1	P02462-1
COL4A1	ENST00000650424.1 linkuse as main transcript	c.306+38C>G	intron_variant
COL4A1	ENST00000649720.1 linkuse as main transcript	n.318+38C>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52300

AN:

151974

Hom.:

9845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.399

AC:

95724

AN:

240100

Hom.:

20458

AF XY:

0.397

AC XY:

51959

AN XY:

130772

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.727

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.377

AC:

548568

AN:

1455668

Hom.:

106583

Cov.:

AF XY:

0.377

AC XY:

272532

AN XY:

723496

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.693

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.384

GnomAD4 genome

AF:

0.344

AC:

52302

AN:

152090

Hom.:

9840

Cov.:

AF XY:

0.348

AC XY:

25891

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.728

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.371

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.362

Hom.:

1861

Bravo

AF:

0.346

Asia WGS

AF:

0.512

AC:

1777

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brain small vessel disease 1 with or without ocular anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.11

DANN

Benign

0.47

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