rs10123014

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.1720-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,307,150 control chromosomes in the GnomAD database, including 54,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5657 hom., cov: 26)

Exomes 𝑓: 0.29 ( 48415 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.619

Publications

6 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 9-134753802-T-C is Benign according to our data. Variant chr9-134753802-T-C is described in ClinVar as Benign. ClinVar VariationId is 255056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COL5A1	NM_000093.5 link	c.1720-48T>C	intron_variant	Intron 14 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 link	c.1720-48T>C	intron_variant	Intron 14 of 65		NP_001265003.1
COL5A1	XM_017014266.3 link	c.1720-48T>C	intron_variant	Intron 14 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.1720-48T>C		intron_variant	Intron 14 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4 link	c.1720-48T>C		intron_variant	Intron 14 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

40426

AN:

147064

Hom.:

5647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.271

GnomAD2 exomes

AF:

0.253

AC:

62763

AN:

248174

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.289

AC:

334996

AN:

1159964

Hom.:

48415

Cov.:

AF XY:

0.286

AC XY:

168099

AN XY:

588378

show subpopulations

African (AFR)

AF:

0.300

AC:

8187

AN:

27260

American (AMR)

AF:

0.160

AC:

6784

AN:

42280

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

3866

AN:

22026

East Asian (EAS)

AF:

0.384

AC:

13504

AN:

35178

South Asian (SAS)

AF:

0.211

AC:

17023

AN:

80542

European-Finnish (FIN)

AF:

0.290

AC:

14005

AN:

48286

Middle Eastern (MID)

AF:

0.241

AC:

994

AN:

4120

European-Non Finnish (NFE)

AF:

0.302

AC:

256903

AN:

851852

Other (OTH)

AF:

0.284

AC:

13730

AN:

48420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11550

23100

34651

46201

57751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7818

15636

23454

31272

39090

<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:

0.275

AC:

40449

AN:

147186

Hom.:

5657

Cov.:

AF XY:

0.271

AC XY:

19455

AN XY:

71682

show subpopulations

African (AFR)

AF:

0.286

AC:

11428

AN:

39996

American (AMR)

AF:

0.205

AC:

3036

AN:

14794

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

563

AN:

3422

East Asian (EAS)

AF:

0.358

AC:

1703

AN:

4752

South Asian (SAS)

AF:

0.208

AC:

903

AN:

4350

European-Finnish (FIN)

AF:

0.276

AC:

2706

AN:

9796

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19103

AN:

66858

Other (OTH)

AF:

0.268

AC:

544

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

1434

2868

4301

5735

7169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.258

Hom.:

969

Bravo

AF:

0.271

Asia WGS

AF:

0.232

AC:

807

AN:

3476

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

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

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

-0.91

CADD

Benign

2.4

(source)

DANN

Benign

0.35

PhyloP100

-0.62

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