rs10776910

Variant names:

Variant summary

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

The NM_000093.5(COL5A1):c.4176+35A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,593,238 control chromosomes in the GnomAD database, including 143,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17317 hom., cov: 33)

Exomes 𝑓: 0.42 ( 126586 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.10

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=-0.93).

BP6

Variant 9-134817114-A-C is Benign according to our data. Variant chr9-134817114-A-C is described in ClinVar as [Benign]. Clinvar id is 255085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4176+35A>C	intron_variant	Intron 53 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.4176+35A>C	intron_variant	Intron 53 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4176+35A>C	intron_variant	Intron 53 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.4176+35A>C		intron_variant	Intron 53 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.4176+35A>C		intron_variant	Intron 53 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70830

AN:

151884

Hom.:

17291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.453

GnomAD3 exomes

AF:

0.414

AC:

103242

AN:

249602

Hom.:

21964

AF XY:

0.407

AC XY:

55041

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.476

Gnomad SAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.415

AC:

598688

AN:

1441236

Hom.:

126586

Cov.:

AF XY:

0.414

AC XY:

297030

AN XY:

718112

show subpopulations

Gnomad4 AFR exome

AF:

0.631

Gnomad4 AMR exome

AF:

0.374

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.418

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.466

AC:

70908

AN:

152002

Hom.:

17317

Cov.:

AF XY:

0.459

AC XY:

34124

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.450

Hom.:

4863

Bravo

AF:

0.479

Asia WGS

AF:

0.402

AC:

1400

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.41

DANN

Benign

0.40

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