9-134785950-G-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.2593-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,555,858 control chromosomes in the GnomAD database, including 3,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 714 hom., cov: 33)

Exomes 𝑓: 0.053 ( 2412 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.131

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=-0.89).

BP6

Variant 9-134785950-G-A is Benign according to our data. Variant chr9-134785950-G-A is described in ClinVar as Benign. ClinVar VariationId is 255066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.2593-45G>A	intron_variant	Intron 30 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.2593-45G>A	intron_variant	Intron 30 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.2593-45G>A	intron_variant	Intron 30 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2593-45G>A		intron_variant	Intron 30 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.2593-45G>A		intron_variant	Intron 30 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12090

AN:

152104

Hom.:

714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0309

Gnomad FIN

AF:

0.0556

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0481

Gnomad OTH

AF:

0.0689

GnomAD2 exomes

AF:

0.0569

AC:

13727

AN:

241424

AF XY:

0.0536

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0581

Gnomad EAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0592

Gnomad NFE exome

AF:

0.0476

Gnomad OTH exome

AF:

0.0487

GnomAD4 exome

AF:

0.0530

AC:

74404

AN:

1403636

Hom.:

2412

Cov.:

AF XY:

0.0522

AC XY:

36621

AN XY:

701322

show subpopulations

African (AFR)

AF:

0.166

AC:

5350

AN:

32290

American (AMR)

AF:

0.0247

AC:

1086

AN:

44028

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

1511

AN:

25704

East Asian (EAS)

AF:

0.111

AC:

4341

AN:

39204

South Asian (SAS)

AF:

0.0337

AC:

2830

AN:

83924

European-Finnish (FIN)

AF:

0.0567

AC:

2986

AN:

52676

Middle Eastern (MID)

AF:

0.0524

AC:

298

AN:

5690

European-Non Finnish (NFE)

AF:

0.0494

AC:

52477

AN:

1061590

Other (OTH)

AF:

0.0602

AC:

3525

AN:

58530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3543

7086

10629

14172

17715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2098

4196

6294

8392

10490

<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:

0.0795

AC:

12100

AN:

152222

Hom.:

714

Cov.:

AF XY:

0.0771

AC XY:

5740

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.159

AC:

6611

AN:

41516

American (AMR)

AF:

0.0339

AC:

519

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3466

East Asian (EAS)

AF:

0.117

AC:

607

AN:

5172

South Asian (SAS)

AF:

0.0303

AC:

146

AN:

4822

European-Finnish (FIN)

AF:

0.0556

AC:

590

AN:

10606

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0481

AC:

3272

AN:

68024

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

562

1124

1685

2247

2809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0332

Hom.:

Bravo

AF:

0.0821

Asia WGS

AF:

0.0790

AC:

276

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 14, 2018

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. -

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

-0.89

CADD

Benign

0.41

(source)

DANN

Benign

0.82

PhyloP100

0.13

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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