Variant 13-110172627-C-G 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.3556+93G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,250,774 control chromosomes in the GnomAD database, including 81,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9064 hom., cov: 33)

Exomes 𝑓: 0.36 ( 72714 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.531

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 13-110172627-C-G is Benign according to our data. Variant chr13-110172627-C-G is described in ClinVar as [Benign]. Clinvar id is 1261484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 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.3556+93G>C		intron_variant		ENST00000375820.10	NP_001836.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 linkuse as main transcript	c.3556+93G>C		intron_variant		1	NM_001845.6	ENSP00000364979	P1	P02462-1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52263

AN:

151970

Hom.:

9047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.360

AC:

396049

AN:

1098686

Hom.:

72714

AF XY:

0.361

AC XY:

203308

AN XY:

563756

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.319

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.344

AC:

52313

AN:

152088

Hom.:

9064

Cov.:

AF XY:

0.344

AC XY:

25565

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.361

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.362

Hom.:

1282

Bravo

AF:

0.342

Asia WGS

AF:

0.359

AC:

1246

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

-0.91

CADD

Benign

1.6

DANN

Benign

0.34

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