9-134738741-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000093.5(COL5A1):c.1432-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,606,282 control chromosomes in the GnomAD database, including 215,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25614 hom., cov: 33)

Exomes 𝑓: 0.50 ( 189520 hom. )

Consequence

COL5A1
NM_000093.5 splice_region, intron

Scores

Splicing: ADA: 0.04311

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.130

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-134738741-T-C is Benign according to our data. Variant chr9-134738741-T-C is described in ClinVar as [Benign]. Clinvar id is 136931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134738741-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.1432-5T>C	splice_region_variant, intron_variant	Intron 10 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.1432-5T>C	splice_region_variant, intron_variant	Intron 10 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.1432-5T>C	splice_region_variant, intron_variant	Intron 10 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.1432-5T>C		splice_region_variant, intron_variant	Intron 10 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.1432-5T>C		splice_region_variant, intron_variant	Intron 10 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85560

AN:

151886

Hom.:

25585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.481

AC:

120732

AN:

250958

Hom.:

31226

AF XY:

0.482

AC XY:

65371

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.522

Gnomad SAS exome

AF:

0.484

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.509

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.505

AC:

734045

AN:

1454276

Hom.:

189520

Cov.:

AF XY:

0.503

AC XY:

364440

AN XY:

723930

show subpopulations

Gnomad4 AFR exome

AF:

0.790

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.327

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.506

Gnomad4 NFE exome

AF:

0.512

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.563

AC:

85636

AN:

152006

Hom.:

25614

Cov.:

AF XY:

0.555

AC XY:

41258

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.774

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.505

Gnomad4 SAS

AF:

0.482

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.516

Hom.:

13070

Bravo

AF:

0.562

Asia WGS

AF:

0.467

AC:

1630

AN:

3478

EpiCase

AF:

0.496

EpiControl

AF:

0.495

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 15, 2017

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: c.1432-5T>C in COL5A1 gene is an intronic change that involves a conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing pattern, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.4997 (60614 / 121292chrs tested) including numerous homozygous occurrences. The observed frequencies exceed the maximum expected allele frequency for a pathogenic variant of 0.00003 suggesting that it is a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but is cited as Benign/ Likely Benign by multiple reputable databases/clinical laboratory. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Dec 29, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Ehlers-Danlos syndrome type 7A

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.41

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.043

dbscSNV1_RF

Benign

0.11

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