rs188473199

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000093.5(COL5A1):c.4231-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,600,364 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 13 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Splicing: ADA: 0.00004342

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.0710

Variant links:

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 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=-0.87).

BP6

Variant 9-134818644-G-A is Benign according to our data. Variant chr9-134818644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 136894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0052 (791/152180) while in subpopulation AFR AF= 0.0106 (440/41530). AF 95% confidence interval is 0.00978. There are 3 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 791 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4231-12G>A	intron_variant	Intron 54 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.4231-12G>A	intron_variant	Intron 54 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4231-12G>A	intron_variant	Intron 54 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.4231-12G>A		intron_variant	Intron 54 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.4231-12G>A		intron_variant	Intron 54 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

788

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00288

AC:

667

AN:

231908

Hom.:

AF XY:

0.00275

AC XY:

349

AN XY:

126950

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.00427

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.0000573

Gnomad SAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00263

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00240

AC:

3480

AN:

1448184

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1630

AN XY:

720024

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.00460

Gnomad4 ASJ exome

AF:

0.00409

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.0000583

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00549

GnomAD4 genome

AF:

0.00520

AC:

791

AN:

152180

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

381

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00231

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.00650

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 21, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 21, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome type 7A

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.4

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000043

dbscSNV1_RF

Benign

0.0020

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