9-134842570-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.*267C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 566,286 control chromosomes in the GnomAD database, including 72,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16774 hom., cov: 32)

Exomes 𝑓: 0.51 ( 56219 hom. )

Consequence

COL5A1
NM_000093.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.475

Publications

112 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:

LOC101448202 (HGNC:):

LOC101448202 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=-0.85).

BP6

Variant 9-134842570-C-T is Benign according to our data. Variant chr9-134842570-C-T is described in ClinVar as Benign. ClinVar VariationId is 365746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COL5A1	NM_000093.5 link	c.*267C>T	3_prime_UTR_variant	Exon 66 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 link	c.*267C>T	3_prime_UTR_variant	Exon 66 of 66		NP_001265003.1
LOC101448202	NR_103451.2 link	n.71-22361G>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.*267C>T		3_prime_UTR_variant	Exon 66 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4 link	c.*267C>T		3_prime_UTR_variant	Exon 66 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66502

AN:

152014

Hom.:

16777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.621

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.506

AC:

209564

AN:

414154

Hom.:

56219

Cov.:

AF XY:

0.501

AC XY:

109184

AN XY:

217818

show subpopulations

African (AFR)

AF:

0.195

AC:

2255

AN:

11556

American (AMR)

AF:

0.448

AC:

7513

AN:

16772

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

6448

AN:

12564

East Asian (EAS)

AF:

0.190

AC:

5434

AN:

28608

South Asian (SAS)

AF:

0.420

AC:

18232

AN:

43398

European-Finnish (FIN)

AF:

0.618

AC:

17235

AN:

27872

Middle Eastern (MID)

AF:

0.555

AC:

999

AN:

1800

European-Non Finnish (NFE)

AF:

0.563

AC:

139471

AN:

247874

Other (OTH)

AF:

0.505

AC:

11977

AN:

23710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

4470

8940

13410

17880

22350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.437

AC:

66504

AN:

152132

Hom.:

16774

Cov.:

AF XY:

0.437

AC XY:

32486

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.196

AC:

8129

AN:

41524

American (AMR)

AF:

0.449

AC:

6859

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1772

AN:

3472

East Asian (EAS)

AF:

0.217

AC:

1121

AN:

5160

South Asian (SAS)

AF:

0.434

AC:

2094

AN:

4830

European-Finnish (FIN)

AF:

0.621

AC:

6578

AN:

10586

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38355

AN:

67960

Other (OTH)

AF:

0.478

AC:

1007

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1699

3399

5098

6798

8497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.485

Hom.:

4807

Bravo

AF:

0.412

Asia WGS

AF:

0.347

AC:

1208

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 18, 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

- -

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 type 7A

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.85

CADD

Benign

3.7

(source)

DANN

Benign

0.59

PhyloP100

0.47

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