Variant 13-110192374-C-T 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.1466-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,240,710 control chromosomes in the GnomAD database, including 135,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13351 hom., cov: 32)

Exomes 𝑓: 0.47 ( 122185 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0650

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

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-110192374-C-T is Benign according to our data. Variant chr13-110192374-C-T is described in ClinVar as [Benign]. Clinvar id is 1292612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.534 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.1466-90G>A		intron_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2 linkuse as main transcript	c.1466-90G>A		intron_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.1466-90G>A	intron_variant	1	NM_001845.6	ENSP00000364979	P1	P02462-1
COL4A1	ENST00000543140.6 linkuse as main transcript	c.1466-90G>A	intron_variant	1		ENSP00000443348		P02462-2
COL4A1	ENST00000649738.1 linkuse as main transcript	n.1596-90G>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62588

AN:

151762

Hom.:

13356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.369

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.464

GnomAD4 exome

AF:

0.470

AC:

511773

AN:

1088830

Hom.:

122185

AF XY:

0.473

AC XY:

263101

AN XY:

555830

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.510

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.538

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.475

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.412

AC:

62585

AN:

151880

Hom.:

13351

Cov.:

AF XY:

0.412

AC XY:

30554

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.485

Gnomad4 SAS

AF:

0.551

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.465

Gnomad4 OTH

AF:

0.463

Alfa

AF:

0.448

Hom.:

15927

Bravo

AF:

0.400

Asia WGS

AF:

0.510

AC:

1772

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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.1

DANN

Benign

0.33

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