chr9-134780166-C-T

Position:

chr9-134780166-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.2430+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,611,542 control chromosomes in the GnomAD database, including 163,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12189 hom., cov: 33)

Exomes 𝑓: 0.45 ( 151569 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.76

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:

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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=-0.96).

BP6

Variant 9-134780166-C-T is Benign according to our data. Variant chr9-134780166-C-T is described in ClinVar as [Benign]. Clinvar id is 136866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134780166-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL5A1	NM_000093.5 linkuse as main transcript	c.2430+20C>T	intron_variant	ENST00000371817.8
COL5A1	NM_001278074.1 linkuse as main transcript	c.2430+20C>T	intron_variant
COL5A1	XM_017014266.3 linkuse as main transcript	c.2430+20C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.2430+20C>T		intron_variant		1	NM_000093.5	P4	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.2430+20C>T		intron_variant		2		A2	P20908-2

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55888

AN:

151986

Hom.:

12184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.650

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.0810

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.401

GnomAD3 exomes

AF:

0.418

AC:

104628

AN:

250528

Hom.:

24214

AF XY:

0.426

AC XY:

57849

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.0660

Gnomad SAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.461

Gnomad OTH exome

AF:

0.447

GnomAD4 exome

AF:

0.447

AC:

651994

AN:

1459438

Hom.:

151569

Cov.:

AF XY:

0.448

AC XY:

325358

AN XY:

726128

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.0743

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.489

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.424

GnomAD4 genome

AF:

0.368

AC:

55900

AN:

152104

Hom.:

12189

Cov.:

AF XY:

0.371

AC XY:

27607

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.495

Gnomad4 EAS

AF:

0.0803

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.489

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.450

Hom.:

22445

Bravo

AF:

0.358

Asia WGS

AF:

0.275

AC:

956

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Fibromuscular dysplasia, multifocal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

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.2430+20C>T variant involves the alteration of a non-conserved intronic nucleotide. Although Mutation Taster was down at the time of this scoring, 5/5 splice prediction tools predict no significant impact on normal splicing and has no significant effect on ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 49278/120530 control chromosomes (11250 homozygotes) at a frequency of 0.4088443, which is approximately 327075 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.040

DANN

Benign

0.58

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