chr9-134761890-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, classic type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
Ehlers-Danlos syndrome, classic type, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
arterial disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COL5A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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	Exon rank	MANE	Protein
COL5A1	NM_000093.5 link	c.1936-35C>A	intron_variant	Intron 18 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 link	c.1936-35C>A	intron_variant	Intron 18 of 65		NP_001265003.1
COL5A1	XM_017014266.3 link	c.1936-35C>A	intron_variant	Intron 18 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.1936-35C>A		intron_variant	Intron 18 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4 link	c.1936-35C>A		intron_variant	Intron 18 of 65	2		ENSP00000360885.4

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

GnomAD2 exomes

AF:

0.116

AC:

28964

AN:

250734

AF XY:

0.104

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 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

African (AFR)

AF:

0.290

AC:

9667

AN:

33384

American (AMR)

AF:

0.242

AC:

10819

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0854

AC:

2230

AN:

26098

East Asian (EAS)

AF:

0.270

AC:

10694

AN:

39670

South Asian (SAS)

AF:

0.118

AC:

10148

AN:

86196

European-Finnish (FIN)

AF:

0.0344

AC:

1814

AN:

52722

Middle Eastern (MID)

AF:

0.0823

AC:

474

AN:

5756

European-Non Finnish (NFE)

AF:

0.0367

AC:

40741

AN:

1108762

Other (OTH)

AF:

0.0795

AC:

4790

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4413

8826

13240

17653

22066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1932

3864

5796

7728

9660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.131

AC:

20008

AN:

152250

Hom.:

2264

Cov.:

AF XY:

0.132

AC XY:

9804

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.286

AC:

11871

AN:

41518

American (AMR)

AF:

0.168

AC:

2570

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

286

AN:

3468

East Asian (EAS)

AF:

0.272

AC:

1408

AN:

5182

South Asian (SAS)

AF:

0.120

AC:

581

AN:

4828

European-Finnish (FIN)

AF:

0.0316

AC:

335

AN:

10616

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0394

AC:

2677

AN:

68022

Other (OTH)

AF:

0.108

AC:

228

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

798

1595

2393

3190

3988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.106

Hom.:

397

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

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Mar 15, 2022

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

-0.85

CADD

Benign

2.8

(source)

DANN

Benign

0.68

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over