chr9-134796811-A-G

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.2845-37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,600,080 control chromosomes in the GnomAD database, including 177,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18434 hom., cov: 33)

Exomes 𝑓: 0.46 ( 158759 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.300

Publications

8 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=-0.98).

BP6

Variant 9-134796811-A-G is Benign according to our data. Variant chr9-134796811-A-G is described in ClinVar as Benign. ClinVar VariationId is 255072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.2845-37A>G	intron_variant	Intron 35 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.2845-37A>G	intron_variant	Intron 35 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.2845-37A>G	intron_variant	Intron 35 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2845-37A>G		intron_variant	Intron 35 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.2845-37A>G		intron_variant	Intron 35 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

74000

AN:

151858

Hom.:

18424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.474

GnomAD2 exomes

AF:

0.482

AC:

120722

AN:

250660

AF XY:

0.477

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.498

Gnomad EAS exome

AF:

0.754

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.465

AC:

672713

AN:

1448104

Hom.:

158759

Cov.:

AF XY:

0.465

AC XY:

335299

AN XY:

721446

show subpopulations

African (AFR)

AF:

0.551

AC:

18325

AN:

33232

American (AMR)

AF:

0.446

AC:

19941

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

12810

AN:

26042

East Asian (EAS)

AF:

0.715

AC:

28328

AN:

39634

South Asian (SAS)

AF:

0.467

AC:

40138

AN:

85962

European-Finnish (FIN)

AF:

0.417

AC:

22197

AN:

53288

Middle Eastern (MID)

AF:

0.507

AC:

2911

AN:

5742

European-Non Finnish (NFE)

AF:

0.454

AC:

499467

AN:

1099618

Other (OTH)

AF:

0.477

AC:

28596

AN:

59906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

20507

41014

61522

82029

102536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14998

29996

44994

59992

74990

<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:

0.487

AC:

74055

AN:

151976

Hom.:

18434

Cov.:

AF XY:

0.485

AC XY:

35999

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.554

AC:

22981

AN:

41450

American (AMR)

AF:

0.423

AC:

6461

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

1728

AN:

3466

East Asian (EAS)

AF:

0.741

AC:

3829

AN:

5164

South Asian (SAS)

AF:

0.464

AC:

2235

AN:

4812

European-Finnish (FIN)

AF:

0.417

AC:

4404

AN:

10560

Middle Eastern (MID)

AF:

0.469

AC:

137

AN:

292

European-Non Finnish (NFE)

AF:

0.458

AC:

31090

AN:

67942

Other (OTH)

AF:

0.472

AC:

994

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1984

3968

5953

7937

9921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.467

Hom.:

65516

Bravo

AF:

0.492

Asia WGS

AF:

0.580

AC:

2014

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 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. -

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

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

-0.98

CADD

Benign

1.9

(source)

DANN

Benign

0.42

PhyloP100

0.30

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