dbSNP rs1213026: COL4A1:c.3949+143T>C (chr13-110167015-A-G) – 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.3949+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 768,236 control chromosomes in the GnomAD database, including 162,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29757 hom., cov: 33)

Exomes 𝑓: 0.65 ( 133101 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0430

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=-0.85).

BP6

Variant 13-110167015-A-G is Benign according to our data. Variant chr13-110167015-A-G is described in ClinVar as [Benign]. Clinvar id is 1236593.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A1	NM_001845.6 link	c.3949+143T>C		intron_variant	Intron 44 of 51	ENST00000375820.10	NP_001836.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 link	c.3949+143T>C		intron_variant	Intron 44 of 51	1	NM_001845.6	ENSP00000364979.4		P02462-1
COL4A1	ENST00000650424.1 link	c.103+143T>C		intron_variant	Intron 2 of 9			ENSP00000497477.2		A0A3B3ISV3

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94346

AN:

151978

Hom.:

29752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.615

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.616

GnomAD4 exome

AF:

0.655

AC:

403497

AN:

616140

Hom.:

133101

AF XY:

0.655

AC XY:

218283

AN XY:

333148

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.595

Gnomad4 SAS exome

AF:

0.662

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.653

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.621

AC:

94391

AN:

152096

Hom.:

29757

Cov.:

AF XY:

0.626

AC XY:

46531

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.613

Gnomad4 EAS

AF:

0.614

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.725

Gnomad4 NFE

AF:

0.657

Gnomad4 OTH

AF:

0.620

Alfa

AF:

0.644

Hom.:

6166

Bravo

AF:

0.612

Asia WGS

AF:

0.669

AC:

2329

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 29, 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

-0.85

CADD

Benign

1.9

DANN

Benign

0.26

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