9-134789254-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.2700+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 1,526,274 control chromosomes in the GnomAD database, including 1,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 150 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1692 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

Publications

4 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=-0.99).

BP6

Variant 9-134789254-C-T is Benign according to our data. Variant chr9-134789254-C-T is described in ClinVar as Benign. ClinVar VariationId is 255068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COL5A1	NM_000093.5 link	c.2700+46C>T	intron_variant	Intron 32 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 link	c.2700+46C>T	intron_variant	Intron 32 of 65		NP_001265003.1
COL5A1	XM_017014266.3 link	c.2700+46C>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.2700+46C>T		intron_variant	Intron 32 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4 link	c.2700+46C>T		intron_variant	Intron 32 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5811

AN:

152128

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0782

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0417

AC:

9961

AN:

238944

AF XY:

0.0421

show subpopulations

Gnomad AFR exome

AF:

0.00792

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.000672

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0594

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0481

AC:

66090

AN:

1374028

Hom.:

1692

Cov.:

AF XY:

0.0475

AC XY:

32685

AN XY:

687932

show subpopulations

African (AFR)

AF:

0.00766

AC:

243

AN:

31718

American (AMR)

AF:

0.0210

AC:

926

AN:

44088

Ashkenazi Jewish (ASJ)

AF:

0.0427

AC:

1085

AN:

25420

East Asian (EAS)

AF:

0.000383

AC:

AN:

39206

South Asian (SAS)

AF:

0.0196

AC:

1640

AN:

83872

European-Finnish (FIN)

AF:

0.0748

AC:

3812

AN:

50968

Middle Eastern (MID)

AF:

0.0417

AC:

233

AN:

5582

European-Non Finnish (NFE)

AF:

0.0537

AC:

55641

AN:

1035836

Other (OTH)

AF:

0.0435

AC:

2495

AN:

57338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3222

6443

9665

12886

16108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1926

3852

5778

7704

9630

<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:

0.0382

AC:

5810

AN:

152246

Hom.:

150

Cov.:

AF XY:

0.0386

AC XY:

2869

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00862

AC:

358

AN:

41554

American (AMR)

AF:

0.0277

AC:

424

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5178

South Asian (SAS)

AF:

0.0195

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0782

AC:

828

AN:

10590

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0559

AC:

3805

AN:

68016

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

283

566

850

1133

1416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0465

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.0170

AC:

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 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

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

-0.99

CADD

Benign

0.074

(source)

DANN

Benign

0.75

PhyloP100

-1.3

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