rs13297647

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.3475-36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,612,244 control chromosomes in the GnomAD database, including 2,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 144 hom., cov: 34)

Exomes 𝑓: 0.049 ( 1917 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.104

Publications

1 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=-0.84).

BP6

Variant 9-134810219-A-C is Benign according to our data. Variant chr9-134810219-A-C is described in ClinVar as Benign. ClinVar VariationId is 255077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 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.3475-36A>C		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.3475-36A>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.3475-36A>C	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.3475-36A>C	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.3466-36A>C	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5849

AN:

152256

Hom.:

144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00945

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0740

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0573

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0409

AC:

10269

AN:

251070

AF XY:

0.0411

show subpopulations

Gnomad AFR exome

AF:

0.00802

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0411

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0710

Gnomad NFE exome

AF:

0.0591

Gnomad OTH exome

AF:

0.0459

GnomAD4 exome

AF:

0.0493

AC:

71950

AN:

1459870

Hom.:

1917

Cov.:

AF XY:

0.0486

AC XY:

35287

AN XY:

726394

show subpopulations

African (AFR)

AF:

0.00816

AC:

273

AN:

33444

American (AMR)

AF:

0.0202

AC:

902

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0408

AC:

1067

AN:

26132

East Asian (EAS)

AF:

0.000277

AC:

AN:

39694

South Asian (SAS)

AF:

0.0171

AC:

1477

AN:

86222

European-Finnish (FIN)

AF:

0.0707

AC:

3776

AN:

53374

Middle Eastern (MID)

AF:

0.0347

AC:

200

AN:

5766

European-Non Finnish (NFE)

AF:

0.0555

AC:

61583

AN:

1110226

Other (OTH)

AF:

0.0441

AC:

2661

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

3282

6563

9845

13126

16408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2200

4400

6600

8800

11000

<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:

0.0384

AC:

5848

AN:

152374

Hom.:

144

Cov.:

AF XY:

0.0382

AC XY:

2847

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00943

AC:

392

AN:

41588

American (AMR)

AF:

0.0268

AC:

410

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

159

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0176

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0740

AC:

786

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0573

AC:

3896

AN:

68038

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

314

628

943

1257

1571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0463

Hom.:

Bravo

AF:

0.0344

Asia WGS

AF:

0.0150

AC:

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

-0.84

CADD

Benign

2.9

(source)

DANN

Benign

0.51

PhyloP100

0.10

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