9-134728628-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.787-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,611,774 control chromosomes in the GnomAD database, including 163,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13446 hom., cov: 33)

Exomes 𝑓: 0.45 ( 150138 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.41

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=-0.91).

BP6

Variant 9-134728628-C-T is Benign according to our data. Variant chr9-134728628-C-T is described in ClinVar as [Benign]. Clinvar id is 255100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.787-42C>T	intron_variant	Intron 5 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.787-42C>T	intron_variant	Intron 5 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.787-42C>T	intron_variant	Intron 5 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.787-42C>T		intron_variant	Intron 5 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.787-42C>T		intron_variant	Intron 5 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60927

AN:

151930

Hom.:

13429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.450

GnomAD2 exomes

AF:

0.480

AC:

120009

AN:

250212

AF XY:

0.476

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.627

Gnomad EAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.443

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.448

AC:

654597

AN:

1459726

Hom.:

150138

Cov.:

AF XY:

0.449

AC XY:

326277

AN XY:

726224

show subpopulations

African (AFR)

AF:

0.207

AC:

6922

AN:

33458

American (AMR)

AF:

0.694

AC:

31022

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

16407

AN:

26128

East Asian (EAS)

AF:

0.470

AC:

18659

AN:

39684

South Asian (SAS)

AF:

0.471

AC:

40582

AN:

86228

European-Finnish (FIN)

AF:

0.463

AC:

24239

AN:

52330

Middle Eastern (MID)

AF:

0.494

AC:

2843

AN:

5758

European-Non Finnish (NFE)

AF:

0.438

AC:

486493

AN:

1111064

Other (OTH)

AF:

0.454

AC:

27430

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

17762

35525

53287

71050

88812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.401

AC:

60979

AN:

152048

Hom.:

13446

Cov.:

AF XY:

0.409

AC XY:

30399

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.220

AC:

9139

AN:

41492

American (AMR)

AF:

0.576

AC:

8811

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2168

AN:

3466

East Asian (EAS)

AF:

0.481

AC:

2468

AN:

5136

South Asian (SAS)

AF:

0.468

AC:

2249

AN:

4808

European-Finnish (FIN)

AF:

0.462

AC:

4893

AN:

10580

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29854

AN:

67950

Other (OTH)

AF:

0.453

AC:

959

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1753

3506

5260

7013

8766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.434

Hom.:

2891

Bravo

AF:

0.402

Asia WGS

AF:

0.509

AC:

1764

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

-0.91

CADD

Benign

0.046

(source)

DANN

Benign

0.91

PhyloP100

-2.4

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

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

9-134728628-C-T

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