9-134795060-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.2701-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,609,636 control chromosomes in the GnomAD database, including 281,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33155 hom., cov: 32)

Exomes 𝑓: 0.58 ( 248811 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.278

Publications

14 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=-0.66).

BP6

Variant 9-134795060-C-T is Benign according to our data. Variant chr9-134795060-C-T is described in ClinVar as Benign. ClinVar VariationId is 255069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.2701-22C>T	intron_variant	Intron 32 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.2701-22C>T	intron_variant	Intron 32 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.2701-22C>T	intron_variant	Intron 32 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2701-22C>T		intron_variant	Intron 32 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.2701-22C>T		intron_variant	Intron 32 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98523

AN:

151908

Hom.:

33113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.631

GnomAD2 exomes

AF:

0.604

AC:

151063

AN:

250244

AF XY:

0.597

show subpopulations

Gnomad AFR exome

AF:

0.844

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.834

Gnomad FIN exome

AF:

0.552

Gnomad NFE exome

AF:

0.574

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.580

AC:

845558

AN:

1457608

Hom.:

248811

Cov.:

AF XY:

0.580

AC XY:

420389

AN XY:

725372

show subpopulations

African (AFR)

AF:

0.848

AC:

28370

AN:

33442

American (AMR)

AF:

0.534

AC:

23868

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15912

AN:

26112

East Asian (EAS)

AF:

0.800

AC:

31763

AN:

39684

South Asian (SAS)

AF:

0.568

AC:

48961

AN:

86174

European-Finnish (FIN)

AF:

0.548

AC:

29173

AN:

53228

Middle Eastern (MID)

AF:

0.604

AC:

3477

AN:

5760

European-Non Finnish (NFE)

AF:

0.566

AC:

627660

AN:

1108256

Other (OTH)

AF:

0.604

AC:

36374

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

17913

35826

53738

71651

89564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17498

34996

52494

69992

87490

<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:

0.649

AC:

98624

AN:

152028

Hom.:

33155

Cov.:

AF XY:

0.645

AC XY:

47896

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.832

AC:

34494

AN:

41468

American (AMR)

AF:

0.542

AC:

8280

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2118

AN:

3470

East Asian (EAS)

AF:

0.822

AC:

4240

AN:

5158

South Asian (SAS)

AF:

0.574

AC:

2757

AN:

4806

European-Finnish (FIN)

AF:

0.553

AC:

5838

AN:

10554

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.574

AC:

39049

AN:

67980

Other (OTH)

AF:

0.630

AC:

1331

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1675

3350

5024

6699

8374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.631

Hom.:

13308

Bravo

AF:

0.659

Asia WGS

AF:

0.720

AC:

2503

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

-0.66

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.28

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