rs11103502

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.1827+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,609,864 control chromosomes in the GnomAD database, including 27,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2096 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25444 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.35

Publications

7 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 9-134754371-G-A is Benign according to our data. Variant chr9-134754371-G-A is described in ClinVar as Benign. ClinVar VariationId is 255057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.1827+45G>A	intron_variant	Intron 16 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.1827+45G>A	intron_variant	Intron 16 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.1827+45G>A	intron_variant	Intron 16 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.1827+45G>A		intron_variant	Intron 16 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.1827+45G>A		intron_variant	Intron 16 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23455

AN:

152080

Hom.:

2094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.153

GnomAD2 exomes

AF:

0.169

AC:

42062

AN:

249332

AF XY:

0.170

show subpopulations

Gnomad AFR exome

AF:

0.0897

Gnomad AMR exome

AF:

0.0919

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.182

AC:

265200

AN:

1457666

Hom.:

25444

Cov.:

AF XY:

0.181

AC XY:

131104

AN XY:

725430

show subpopulations

African (AFR)

AF:

0.0842

AC:

2811

AN:

33398

American (AMR)

AF:

0.0963

AC:

4304

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2813

AN:

26102

East Asian (EAS)

AF:

0.355

AC:

14077

AN:

39672

South Asian (SAS)

AF:

0.144

AC:

12375

AN:

86194

European-Finnish (FIN)

AF:

0.187

AC:

9893

AN:

52838

Middle Eastern (MID)

AF:

0.146

AC:

841

AN:

5748

European-Non Finnish (NFE)

AF:

0.187

AC:

207666

AN:

1108746

Other (OTH)

AF:

0.173

AC:

10420

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

12050

24100

36151

48201

60251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7328

14656

21984

29312

36640

<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:

0.154

AC:

23446

AN:

152198

Hom.:

2096

Cov.:

AF XY:

0.155

AC XY:

11551

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0873

AC:

3630

AN:

41576

American (AMR)

AF:

0.122

AC:

1860

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

390

AN:

3472

East Asian (EAS)

AF:

0.344

AC:

1764

AN:

5128

South Asian (SAS)

AF:

0.134

AC:

645

AN:

4816

European-Finnish (FIN)

AF:

0.188

AC:

1996

AN:

10596

Middle Eastern (MID)

AF:

0.151

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.184

AC:

12485

AN:

67994

Other (OTH)

AF:

0.151

AC:

320

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

991

1982

2972

3963

4954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.163

Hom.:

680

Bravo

AF:

0.150

Asia WGS

AF:

0.180

AC:

625

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

0.0040

(source)

DANN

Benign

0.62

PhyloP100

-4.3

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