NM_000093.5:c.5067+20C>G

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.5067+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,548,826 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 56 hom., cov: 34)

Exomes 𝑓: 0.0018 ( 60 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.97

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:

LOC101448202 (HGNC:):

LOC101448202 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 9-134825924-C-G is Benign according to our data. Variant chr9-134825924-C-G is described in ClinVar as [Benign]. Clinvar id is 136907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134825924-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.5067+20C>G	intron_variant	Intron 63 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.5067+20C>G	intron_variant	Intron 63 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.5067+20C>G	intron_variant	Intron 63 of 64		XP_016869755.1
LOC101448202	NR_103451.2 link	n.71-5715G>C	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL5A1	ENST00000371817.8 link	c.5067+20C>G	intron_variant	Intron 63 of 65	1	NM_000093.5	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4 link	c.5067+20C>G	intron_variant	Intron 63 of 65	2		ENSP00000360885.4	P20908-2H7BY82
COL5A1	ENST00000460264.5 link	n.535+20C>G	intron_variant	Intron 4 of 4	3
COL5A1	ENST00000465877.1 link	n.247+20C>G	intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2381

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000558

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00441

AC:

1106

AN:

250642

Hom.:

AF XY:

0.00310

AC XY:

420

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0549

Gnomad AMR exome

AF:

0.00472

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00179

AC:

2494

AN:

1396474

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1070

AN XY:

698310

show subpopulations

Gnomad4 AFR exome

AF:

0.0542

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000826

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.0157

AC:

2389

AN:

152352

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1089

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0541

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000558

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00735

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Apr 15, 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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 11, 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

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.072

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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