9-134750631-C-T

Position:

chr9-134750631-C-T

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+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,458 control chromosomes in the GnomAD database, including 9,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 621 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8699 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.911

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=-0.81).

BP6

Variant 9-134750631-C-T is Benign according to our data. Variant chr9-134750631-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134750631-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
COL5A1	NM_000093.5 linkuse as main transcript	c.1569+15C>T	intron_variant	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 linkuse as main transcript	c.1569+15C>T	intron_variant		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 linkuse as main transcript	c.1569+15C>T	intron_variant		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.1569+15C>T		intron_variant		1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.1569+15C>T		intron_variant		2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0769

AC:

11693

AN:

152140

Hom.:

621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0823

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.0803

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0915

GnomAD3 exomes

AF:

0.0812

AC:

20364

AN:

250778

Hom.:

1156

AF XY:

0.0828

AC XY:

11242

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0588

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0345

Gnomad FIN exome

AF:

0.0789

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.0909

GnomAD4 exome

AF:

0.103

AC:

150276

AN:

1460200

Hom.:

8699

Cov.:

AF XY:

0.101

AC XY:

73644

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.0604

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0796

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.0910

GnomAD4 genome

AF:

0.0768

AC:

11688

AN:

152258

Hom.:

621

Cov.:

AF XY:

0.0747

AC XY:

5563

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.0803

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.0905

Alfa

AF:

0.0641

Hom.:

105

Bravo

AF:

0.0767

Asia WGS

AF:

0.0140

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:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2012	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -

Fibromuscular dysplasia, multifocal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Ehlers-Danlos syndrome type 7A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely 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

-0.81

CADD

Benign

0.26

DANN

Benign

0.57

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