9-134750631-C-T

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.1569+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,458 control chromosomes in the GnomAD database, including 9,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 621 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8699 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.911

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=-0.81).

BP6

Variant 9-134750631-C-T is Benign according to our data. Variant chr9-134750631-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.1569+15C>T	intron_variant	Intron 12 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.1569+15C>T	intron_variant	Intron 12 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.1569+15C>T	intron_variant	Intron 12 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.1569+15C>T		intron_variant	Intron 12 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.1569+15C>T		intron_variant	Intron 12 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0769

AC:

11693

AN:

152140

Hom.:

621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0823

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.0803

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0915

GnomAD2 exomes

AF:

0.0812

AC:

20364

AN:

250778

AF XY:

0.0828

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0588

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0789

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.0909

GnomAD4 exome

AF:

0.103

AC:

150276

AN:

1460200

Hom.:

8699

Cov.:

AF XY:

0.101

AC XY:

73644

AN XY:

726430

show subpopulations

African (AFR)

AF:

0.0166

AC:

557

AN:

33474

American (AMR)

AF:

0.0604

AC:

2702

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4071

AN:

26128

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0359

AC:

3100

AN:

86246

European-Finnish (FIN)

AF:

0.0796

AC:

4186

AN:

52580

Middle Eastern (MID)

AF:

0.0839

AC:

484

AN:

5766

European-Non Finnish (NFE)

AF:

0.117

AC:

129676

AN:

1111222

Other (OTH)

AF:

0.0910

AC:

5495

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7136

14273

21409

28546

35682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4618

9236

13854

18472

23090

<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:

0.0768

AC:

11688

AN:

152258

Hom.:

621

Cov.:

AF XY:

0.0747

AC XY:

5563

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0210

AC:

873

AN:

41554

American (AMR)

AF:

0.0822

AC:

1258

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

560

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.0272

AC:

131

AN:

4824

European-Finnish (FIN)

AF:

0.0803

AC:

853

AN:

10622

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7741

AN:

68008

Other (OTH)

AF:

0.0905

AC:

191

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

543

1086

1630

2173

2716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0685

Hom.:

322

Bravo

AF:

0.0767

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 type 7A

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.26

(source)

DANN

Benign

0.57

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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