rs13301426

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2646+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,593,512 control chromosomes in the GnomAD database, including 4,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 430 hom., cov: 33)

Exomes 𝑓: 0.072 ( 3839 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.11

Publications

8 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=-0.91).

BP6

Variant 9-134786075-C-T is Benign according to our data. Variant chr9-134786075-C-T is described in ClinVar as Benign. ClinVar VariationId is 255067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0771 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.2646+27C>T		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.2646+27C>T		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.2646+27C>T	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.2646+27C>T	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.2637+27C>T	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.0727

AC:

11063

AN:

152150

Hom.:

428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0567

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0424

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0789

Gnomad OTH

AF:

0.0867

GnomAD2 exomes

AF:

0.0704

AC:

15907

AN:

226060

AF XY:

0.0706

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0613

Gnomad EAS exome

AF:

0.0410

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.0828

Gnomad OTH exome

AF:

0.0736

GnomAD4 exome

AF:

0.0716

AC:

103200

AN:

1441244

Hom.:

3839

Cov.:

AF XY:

0.0711

AC XY:

50936

AN XY:

716094

show subpopulations

African (AFR)

AF:

0.0712

AC:

2356

AN:

33112

American (AMR)

AF:

0.0493

AC:

2108

AN:

42782

Ashkenazi Jewish (ASJ)

AF:

0.0636

AC:

1643

AN:

25848

East Asian (EAS)

AF:

0.0273

AC:

1063

AN:

39008

South Asian (SAS)

AF:

0.0441

AC:

3698

AN:

83838

European-Finnish (FIN)

AF:

0.0988

AC:

5172

AN:

52330

Middle Eastern (MID)

AF:

0.0555

AC:

319

AN:

5746

European-Non Finnish (NFE)

AF:

0.0751

AC:

82540

AN:

1098900

Other (OTH)

AF:

0.0721

AC:

4301

AN:

59680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

4367

8735

13102

17470

21837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2976

5952

8928

11904

14880

<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:

0.0727

AC:

11076

AN:

152268

Hom.:

430

Cov.:

AF XY:

0.0724

AC XY:

5388

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0700

AC:

2908

AN:

41554

American (AMR)

AF:

0.0567

AC:

866

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

244

AN:

3472

East Asian (EAS)

AF:

0.0366

AC:

190

AN:

5186

South Asian (SAS)

AF:

0.0425

AC:

205

AN:

4826

European-Finnish (FIN)

AF:

0.103

AC:

1092

AN:

10614

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0789

AC:

5365

AN:

68014

Other (OTH)

AF:

0.0858

AC:

181

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

540

1080

1619

2159

2699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0733

Hom.:

179

Bravo

AF:

0.0704

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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

Fibromuscular dysplasia, multifocal (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.84

PhyloP100

-1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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