Variant chr9-134761890-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000093.5(COL5A1):c.1936-35C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,609,784 control chromosomes in the GnomAD database, including 8,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2264 hom., cov: 33)

Exomes 𝑓: 0.063 ( 6356 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.202

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=-0.85).

BP6

Variant 9-134761890-C-A is Benign according to our data. Variant chr9-134761890-C-A is described in ClinVar as [Benign]. Clinvar id is 255059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COL5A1	NM_000093.5 linkuse as main transcript	c.1936-35C>A	intron_variant	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 linkuse as main transcript	c.1936-35C>A	intron_variant		NP_001265003.1
COL5A1	XM_017014266.3 linkuse as main transcript	c.1936-35C>A	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.1936-35C>A		intron_variant		1	NM_000093.5	ENSP00000360882	P4	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.1936-35C>A		intron_variant		2		ENSP00000360885	A2	P20908-2

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19955

AN:

152132

Hom.:

2257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.0825

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.116

AC:

28964

AN:

250734

Hom.:

3116

AF XY:

0.104

AC XY:

14158

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.0878

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0338

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0876

GnomAD4 exome

AF:

0.0627

AC:

91377

AN:

1457534

Hom.:

6356

Cov.:

AF XY:

0.0624

AC XY:

45262

AN XY:

725312

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.242

Gnomad4 ASJ exome

AF:

0.0854

Gnomad4 EAS exome

AF:

0.270

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0367

Gnomad4 OTH exome

AF:

0.0795

GnomAD4 genome

AF:

0.131

AC:

20008

AN:

152250

Hom.:

2264

Cov.:

AF XY:

0.132

AC XY:

9804

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.0825

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0316

Gnomad4 NFE

AF:

0.0394

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.102

Hom.:

366

Bravo

AF:

0.151

Asia WGS

AF:

0.212

AC:

734

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fibromuscular dysplasia, multifocal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.8

DANN

Benign

0.68

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