9-134730403-C-T

Position:

chr9-134730403-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.1092C>T(p.Pro364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,132 control chromosomes in the GnomAD database, including 2,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 1217 hom., cov: 34)

Exomes 𝑓: 0.023 ( 1759 hom. )

Consequence

COL5A1
NM_000093.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.31

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=-0.65).

BP6

Variant 9-134730403-C-T is Benign according to our data. Variant chr9-134730403-C-T is described in ClinVar as [Benign]. Clinvar id is 136927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134730403-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL5A1	NM_000093.5 linkuse as main transcript	c.1092C>T	p.Pro364=	synonymous_variant	7/66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 linkuse as main transcript	c.1092C>T	p.Pro364=	synonymous_variant	7/66		NP_001265003.1
COL5A1	XM_017014266.3 linkuse as main transcript	c.1092C>T	p.Pro364=	synonymous_variant	7/65		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.1092C>T	p.Pro364=	synonymous_variant	7/66	1	NM_000093.5	ENSP00000360882	P4	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.1092C>T	p.Pro364=	synonymous_variant	7/66	2		ENSP00000360885	A2	P20908-2

Frequencies

GnomAD3 genomes

AF:

0.0787

AC:

11974

AN:

152164

Hom.:

1207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.0578

GnomAD3 exomes

AF:

0.0386

AC:

9704

AN:

251280

Hom.:

730

AF XY:

0.0380

AC XY:

5164

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.00386

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0240

GnomAD4 exome

AF:

0.0226

AC:

33033

AN:

1461850

Hom.:

1759

Cov.:

AF XY:

0.0241

AC XY:

17532

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.0190

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.00259

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.0328

GnomAD4 genome

AF:

0.0788

AC:

12005

AN:

152282

Hom.:

1217

Cov.:

AF XY:

0.0768

AC XY:

5720

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00327

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0464

Hom.:

321

Bravo

AF:

0.0859

Asia WGS

AF:

0.0700

AC:

243

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:9

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 16, 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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.1092C>T (p.Pro364Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 5362/121014 control chromosomes (451 homozygotes) at a frequency of 0.0443089, which is approximately 35447 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. Taken together, this variant is classified as benign. -

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

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2015

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

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

-0.65

CADD

Benign

5.8

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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