Variant 13-110181217-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 ENST00000375820.10(COL4A1):c.2193+75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,453,128 control chromosomes in the GnomAD database, including 92,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8866 hom., cov: 32)

Exomes 𝑓: 0.36 ( 83597 hom. )

Consequence

COL4A1
ENST00000375820.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.35

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=-1.02).

BP6

Variant 13-110181217-C-T is Benign according to our data. Variant chr13-110181217-C-T is described in ClinVar as [Benign]. Clinvar id is 1293320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110181217-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 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.2193+75G>A		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.2193+75G>A		intron_variant		1	NM_001845.6	ENSP00000364979	P1	P02462-1
COL4A1	ENST00000649738.1 linkuse as main transcript	n.2323+75G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51642

AN:

151884

Hom.:

8854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.356

AC:

462816

AN:

1301126

Hom.:

83597

AF XY:

0.357

AC XY:

233195

AN XY:

653972

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.264

Gnomad4 SAS exome

AF:

0.372

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.340

AC:

51692

AN:

152002

Hom.:

8866

Cov.:

AF XY:

0.340

AC XY:

25289

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.363

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.368

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.358

Hom.:

1258

Bravo

AF:

0.338

Asia WGS

AF:

0.362

AC:

1256

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

-1.0

CADD

Benign

0.010

DANN

Benign

0.40

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