9-134842386-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.*83C>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 0.736 in 1,532,632 control chromosomes in the GnomAD database, including 417,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44058 hom., cov: 32)

Exomes 𝑓: 0.73 ( 373297 hom. )

Consequence

COL5A1
NM_000093.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0550

Publications

43 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=-0.88).

BP6

Variant 9-134842386-C-T is Benign according to our data. Variant chr9-134842386-C-T is described in ClinVar as Benign. ClinVar VariationId is 365741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.*83C>T	3_prime_UTR_variant	Exon 66 of 66	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.*83C>T	3_prime_UTR_variant	Exon 66 of 66		NP_001265003.1	B2ZZ86Q59EE7
LOC101448202	NR_103451.2 link	n.71-22177G>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.*83C>T		3_prime_UTR_variant	Exon 66 of 66	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.*83C>T		3_prime_UTR_variant	Exon 66 of 66	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

115116

AN:

152020

Hom.:

44011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.773

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.752

GnomAD4 exome

AF:

0.734

AC:

1013449

AN:

1380494

Hom.:

373297

Cov.:

AF XY:

0.735

AC XY:

505199

AN XY:

687364

show subpopulations

African (AFR)

AF:

0.851

AC:

27248

AN:

32004

American (AMR)

AF:

0.590

AC:

23443

AN:

39754

Ashkenazi Jewish (ASJ)

AF:

0.766

AC:

19361

AN:

25284

East Asian (EAS)

AF:

0.625

AC:

23707

AN:

37948

South Asian (SAS)

AF:

0.756

AC:

62048

AN:

82082

European-Finnish (FIN)

AF:

0.754

AC:

35306

AN:

46832

Middle Eastern (MID)

AF:

0.803

AC:

3473

AN:

4326

European-Non Finnish (NFE)

AF:

0.736

AC:

776124

AN:

1054714

Other (OTH)

AF:

0.743

AC:

42739

AN:

57550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13585

27170

40755

54340

67925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18918

37836

56754

75672

94590

<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:

0.757

AC:

115215

AN:

152138

Hom.:

44058

Cov.:

AF XY:

0.754

AC XY:

56079

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.846

AC:

35128

AN:

41518

American (AMR)

AF:

0.646

AC:

9879

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.770

AC:

2672

AN:

3468

East Asian (EAS)

AF:

0.619

AC:

3178

AN:

5136

South Asian (SAS)

AF:

0.772

AC:

3718

AN:

4818

European-Finnish (FIN)

AF:

0.760

AC:

8061

AN:

10606

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50262

AN:

67982

Other (OTH)

AF:

0.751

AC:

1584

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1390

2780

4170

5560

6950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.744

Hom.:

51540

Bravo

AF:

0.746

Asia WGS

AF:

0.709

AC:

2468

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 16, 2018

GeneDx

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 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

-0.88

CADD

Benign

3.1

(source)

DANN

Benign

0.86

PhyloP100

0.055

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