Variant rs1778817 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.3949+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,531,910 control chromosomes in the GnomAD database, including 326,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29517 hom., cov: 31)

Exomes 𝑓: 0.66 ( 297455 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.32

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=-0.92).

BP6

Variant 13-110167113-G-A is Benign according to our data. Variant chr13-110167113-G-A is described in ClinVar as [Benign]. Clinvar id is 1260831.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110167113-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.661 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.3949+45C>T		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.3949+45C>T		intron_variant		1	NM_001845.6	P1	P02462-1
COL4A1	ENST00000650424.1 linkuse as main transcript	c.105+45C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.620

AC:

93859

AN:

151390

Hom.:

29512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.606

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.610

GnomAD3 exomes

AF:

0.659

AC:

165593

AN:

251232

Hom.:

55076

AF XY:

0.659

AC XY:

89509

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.657

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.655

AC:

904396

AN:

1380400

Hom.:

297455

Cov.:

AF XY:

0.655

AC XY:

453039

AN XY:

691556

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.715

Gnomad4 ASJ exome

AF:

0.602

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.661

Gnomad4 FIN exome

AF:

0.729

Gnomad4 NFE exome

AF:

0.655

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.620

AC:

93905

AN:

151510

Hom.:

29517

Cov.:

AF XY:

0.625

AC XY:

46292

AN XY:

74052

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.670

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.723

Gnomad4 NFE

AF:

0.655

Gnomad4 OTH

AF:

0.614

Alfa

AF:

0.634

Hom.:

6459

Bravo

AF:

0.613

Asia WGS

AF:

0.690

AC:

2401

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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.44

DANN

Benign

0.52

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