rs12685946

Variant names:

Variant summary

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

The NM_000093.5(COL5A1):c.1569+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,612,112 control chromosomes in the GnomAD database, including 49,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7388 hom., cov: 32)

Exomes 𝑓: 0.23 ( 42588 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.73

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=-0.94).

BP6

Variant 9-134750632-A-G is Benign according to our data. Variant chr9-134750632-A-G is described in ClinVar as [Benign]. Clinvar id is 136862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134750632-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.1569+16A>G	intron_variant	Intron 12 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.1569+16A>G	intron_variant	Intron 12 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.1569+16A>G	intron_variant	Intron 12 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.1569+16A>G		intron_variant	Intron 12 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.1569+16A>G		intron_variant	Intron 12 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44030

AN:

151898

Hom.:

7381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.228

AC:

57228

AN:

250686

Hom.:

7576

AF XY:

0.223

AC XY:

30313

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.346

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.235

AC:

342867

AN:

1460096

Hom.:

42588

Cov.:

AF XY:

0.232

AC XY:

168366

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.482

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.290

AC:

44064

AN:

152016

Hom.:

7388

Cov.:

AF XY:

0.285

AC XY:

21218

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.240

Hom.:

916

Bravo

AF:

0.298

Asia WGS

AF:

0.216

AC:

752

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 04, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 02, 2012

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

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0020

DANN

Benign

0.19

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