Variant rs34636935 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.2700+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 1,526,274 control chromosomes in the GnomAD database, including 1,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 150 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1692 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.34

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=-0.99).

BP6

Variant 9-134789254-C-T is Benign according to our data. Variant chr9-134789254-C-T is described in ClinVar as [Benign]. Clinvar id is 255068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL5A1	NM_000093.5 linkuse as main transcript	c.2700+46C>T	intron_variant	ENST00000371817.8
COL5A1	NM_001278074.1 linkuse as main transcript	c.2700+46C>T	intron_variant
COL5A1	XM_017014266.3 linkuse as main transcript	c.2700+46C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.2700+46C>T		intron_variant		1	NM_000093.5	P4	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.2700+46C>T		intron_variant		2		A2	P20908-2

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5811

AN:

152128

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0782

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0417

AC:

9961

AN:

238944

Hom.:

280

AF XY:

0.0421

AC XY:

5475

AN XY:

130004

show subpopulations

Gnomad AFR exome

AF:

0.00792

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.000672

Gnomad SAS exome

AF:

0.0198

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0594

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0481

AC:

66090

AN:

1374028

Hom.:

1692

Cov.:

AF XY:

0.0475

AC XY:

32685

AN XY:

687932

show subpopulations

Gnomad4 AFR exome

AF:

0.00766

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0427

Gnomad4 EAS exome

AF:

0.000383

Gnomad4 SAS exome

AF:

0.0196

Gnomad4 FIN exome

AF:

0.0748

Gnomad4 NFE exome

AF:

0.0537

Gnomad4 OTH exome

AF:

0.0435

GnomAD4 genome

AF:

0.0382

AC:

5810

AN:

152246

Hom.:

150

Cov.:

AF XY:

0.0386

AC XY:

2869

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00862

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0782

Gnomad4 NFE

AF:

0.0559

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0465

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

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

-0.99

CADD

Benign

0.074

DANN

Benign

0.75

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