9-134795141-A-T

Position:

chr9-134795141-A-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.2745+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 1,613,590 control chromosomes in the GnomAD database, including 2,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 175 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2352 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.737

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 9-134795141-A-T is Benign according to our data. Variant chr9-134795141-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 136870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134795141-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
COL5A1	NM_000093.5 linkuse as main transcript	c.2745+15A>T	intron_variant	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 linkuse as main transcript	c.2745+15A>T	intron_variant		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 linkuse as main transcript	c.2745+15A>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.2745+15A>T		intron_variant		1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.2745+15A>T		intron_variant		2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6490

AN:

152088

Hom.:

176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0338

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0753

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0638

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0458

AC:

11508

AN:

251130

Hom.:

367

AF XY:

0.0461

AC XY:

6263

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00937

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0482

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0203

Gnomad FIN exome

AF:

0.0743

Gnomad NFE exome

AF:

0.0661

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0543

AC:

79364

AN:

1461384

Hom.:

2352

Cov.:

AF XY:

0.0535

AC XY:

38895

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00890

Gnomad4 AMR exome

AF:

0.0252

Gnomad4 ASJ exome

AF:

0.0486

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0732

Gnomad4 NFE exome

AF:

0.0609

Gnomad4 OTH exome

AF:

0.0501

GnomAD4 genome

AF:

0.0426

AC:

6487

AN:

152206

Hom.:

175

Cov.:

AF XY:

0.0424

AC XY:

3156

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0753

Gnomad4 NFE

AF:

0.0638

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0521

Hom.:

Bravo

AF:

0.0386

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 15, 2017	Variant summary: The COL5A1 c.2745+15A>T variant involves the alteration of a non-conserved intronic nucleotide. 5/5 splice prediction tools predict elimination of a cryptic donor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 5658/120816 control chromosomes (186 homozygotes) at a frequency of 0.0468315, which is approximately 37465 times the estimated maximal expected allele frequency of a pathogenic COL5A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.7

DANN

Benign

0.69

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