rs3109675

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.1332+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,572,416 control chromosomes in the GnomAD database, including 183,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14956 hom., cov: 34)

Exomes 𝑓: 0.48 ( 168622 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.67

Publications

5 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=-1.04).

BP6

Variant 9-134731709-T-C is Benign according to our data. Variant chr9-134731709-T-C is described in ClinVar as Benign. ClinVar VariationId is 255049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 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.1332+46T>C		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.1332+46T>C		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.1332+46T>C	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.1332+46T>C	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.1323+46T>C	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64395

AN:

152022

Hom.:

14943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.510

AC:

107002

AN:

209666

AF XY:

0.505

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.722

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.501

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.525

GnomAD4 exome

AF:

0.483

AC:

686386

AN:

1420276

Hom.:

168622

Cov.:

AF XY:

0.484

AC XY:

339569

AN XY:

702306

show subpopulations

African (AFR)

AF:

0.212

AC:

6965

AN:

32814

American (AMR)

AF:

0.706

AC:

30302

AN:

42910

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

15870

AN:

23982

East Asian (EAS)

AF:

0.472

AC:

18522

AN:

39252

South Asian (SAS)

AF:

0.476

AC:

38333

AN:

80524

European-Finnish (FIN)

AF:

0.495

AC:

22331

AN:

45126

Middle Eastern (MID)

AF:

0.510

AC:

2828

AN:

5544

European-Non Finnish (NFE)

AF:

0.479

AC:

522866

AN:

1091406

Other (OTH)

AF:

0.483

AC:

28369

AN:

58718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

19515

39031

58546

78062

97577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15726

31452

47178

62904

78630

<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:

0.424

AC:

64442

AN:

152140

Hom.:

14956

Cov.:

AF XY:

0.431

AC XY:

32031

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.227

AC:

9434

AN:

41518

American (AMR)

AF:

0.586

AC:

8973

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

2281

AN:

3472

East Asian (EAS)

AF:

0.482

AC:

2482

AN:

5154

South Asian (SAS)

AF:

0.469

AC:

2261

AN:

4826

European-Finnish (FIN)

AF:

0.494

AC:

5229

AN:

10592

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32334

AN:

67960

Other (OTH)

AF:

0.472

AC:

997

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1839

3678

5518

7357

9196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.460

Hom.:

3253

Bravo

AF:

0.423

Asia WGS

AF:

0.510

AC:

1766

AN:

3476

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)

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

-1.0

CADD

Benign

0.023

(source)

DANN

Benign

0.15

PhyloP100

-3.7

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