rs10858282

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.4176+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,609,628 control chromosomes in the GnomAD database, including 111,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8236 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103374 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.823

Publications

11 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: Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
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=-0.85).

BP6

Variant 9-134817088-T-G is Benign according to our data. Variant chr9-134817088-T-G is described in ClinVar as Benign. ClinVar VariationId is 136891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.4176+9T>G		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.4176+9T>G		intron	N/A	NP_001265003.1	P20908-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.4176+9T>G	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.4176+9T>G	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.4167+9T>G	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48186

AN:

151964

Hom.:

8235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.327

GnomAD2 exomes

AF:

0.343

AC:

86015

AN:

251026

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.373

AC:

543233

AN:

1457548

Hom.:

103374

Cov.:

AF XY:

0.372

AC XY:

269826

AN XY:

725302

show subpopulations

African (AFR)

AF:

0.186

AC:

6209

AN:

33416

American (AMR)

AF:

0.302

AC:

13514

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8644

AN:

26084

East Asian (EAS)

AF:

0.318

AC:

12620

AN:

39668

South Asian (SAS)

AF:

0.305

AC:

26291

AN:

86170

European-Finnish (FIN)

AF:

0.339

AC:

18036

AN:

53246

Middle Eastern (MID)

AF:

0.363

AC:

2074

AN:

5716

European-Non Finnish (NFE)

AF:

0.392

AC:

434412

AN:

1108304

Other (OTH)

AF:

0.356

AC:

21433

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

15945

31889

47834

63778

79723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13312

26624

39936

53248

66560

<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:

0.317

AC:

48202

AN:

152080

Hom.:

8236

Cov.:

AF XY:

0.313

AC XY:

23259

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.191

AC:

7899

AN:

41464

American (AMR)

AF:

0.303

AC:

4633

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1147

AN:

3472

East Asian (EAS)

AF:

0.328

AC:

1693

AN:

5168

South Asian (SAS)

AF:

0.286

AC:

1381

AN:

4826

European-Finnish (FIN)

AF:

0.342

AC:

3614

AN:

10582

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26680

AN:

67970

Other (OTH)

AF:

0.327

AC:

688

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1682

3364

5047

6729

8411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.360

Hom.:

7163

Bravo

AF:

0.311

Asia WGS

AF:

0.288

AC:

1005

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Ehlers-Danlos syndrome, classic type, 1 (2)

not provided (2)

Ehlers-Danlos syndrome type 7A (1)

Fibromuscular dysplasia, multifocal (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.041

(source)

DANN

Benign

0.36

PhyloP100

-0.82

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over