rs13260

Positions:

chr13-110149776-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001845.6(COL4A1):c.*587C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,930 control chromosomes in the GnomAD database, including 1,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1897 hom., cov: 33)

Exomes 𝑓: 0.073 ( 6 hom. )

Consequence

COL4A1
NM_001845.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.11

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:

COL4A1 (HGNC:):

COL4A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-110149776-G-T is Benign according to our data. Variant chr13-110149776-G-T is described in ClinVar as [Benign]. Clinvar id is 311011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 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.*587C>A		3_prime_UTR_variant	52/52	ENST00000375820.10	NP_001836.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL4A1	ENST00000375820 linkuse as main transcript	c.*587C>A	3_prime_UTR_variant	52/52	1	NM_001845.6	ENSP00000364979.4	P02462-1
COL4A1	ENST00000650424.1 linkuse as main transcript	c.*587C>A	3_prime_UTR_variant	10/10			ENSP00000497477.2	A0A3B3ISV3
COL4A1	ENST00000649720.1 linkuse as main transcript	n.1765C>A	non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20987

AN:

151828

Hom.:

1884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.00463

Gnomad SAS

AF:

0.0719

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0918

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.0729

AC:

AN:

988

Hom.:

Cov.:

AF XY:

0.0819

AC XY:

AN XY:

574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0167

Gnomad4 FIN exome

AF:

0.0963

Gnomad4 NFE exome

AF:

0.0551

Gnomad4 OTH exome

AF:

0.0357

GnomAD4 genome

AF:

0.138

AC:

21035

AN:

151942

Hom.:

1897

Cov.:

AF XY:

0.138

AC XY:

10269

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.0839

Gnomad4 NFE

AF:

0.0918

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.0999

Hom.:

896

Bravo

AF:

0.152

Asia WGS

AF:

0.0670

AC:

233

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brain small vessel disease 1 with or without ocular anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Porencephalic cyst

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.41

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