dbSNP rs76574181: COL4A1:c.469-191C>T (chr13-110210403-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001845.6(COL4A1):c.469-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 151,980 control chromosomes in the GnomAD database, including 553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.085 ( 553 hom., cov: 32)

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.55

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 13-110210403-G-A is Benign according to our data. Variant chr13-110210403-G-A is described in ClinVar as [Benign]. Clinvar id is 1293365.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A1	NM_001845.6 link	c.469-191C>T		intron_variant	Intron 8 of 51	ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2 link	c.469-191C>T		intron_variant	Intron 8 of 24		NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 link	c.469-191C>T		intron_variant	Intron 8 of 51	1	NM_001845.6	ENSP00000364979.4		P02462-1

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12909

AN:

151862

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.0646

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.0777

Gnomad SAS

AF:

0.0781

Gnomad FIN

AF:

0.0639

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0809

Gnomad OTH

AF:

0.0846

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0851

AC:

12934

AN:

151980

Hom.:

553

Cov.:

AF XY:

0.0840

AC XY:

6235

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0646

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.0779

Gnomad4 SAS

AF:

0.0776

Gnomad4 FIN

AF:

0.0639

Gnomad4 NFE

AF:

0.0809

Gnomad4 OTH

AF:

0.0842

Alfa

AF:

0.0409

Hom.:

Bravo

AF:

0.0864

Asia WGS

AF:

0.0850

AC:

293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.027

DANN

Benign

0.74

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