rs3811147

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.4447-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,463,016 control chromosomes in the GnomAD database, including 1,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 399 hom., cov: 33)

Exomes 𝑓: 0.013 ( 618 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.777

Publications

3 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:

LOC101448202 (HGNC:):

LOC101448202 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=-0.87).

BP6

Variant 9-134820071-G-A is Benign according to our data. Variant chr9-134820071-G-A is described in ClinVar as [Benign]. Clinvar id is 255088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4447-45G>A	intron_variant	Intron 57 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
LOC101448202	NR_103451.2 link	n.209C>T	non_coding_transcript_exon_variant	Exon 2 of 2
COL5A1	NM_001278074.1 link	c.4447-45G>A	intron_variant	Intron 57 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4447-45G>A	intron_variant	Intron 57 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.4447-45G>A		intron_variant	Intron 57 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.4447-45G>A		intron_variant	Intron 57 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0440

AC:

6702

AN:

152166

Hom.:

395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0877

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00400

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0225

AC:

5647

AN:

250446

AF XY:

0.0200

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0902

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0126

AC:

16568

AN:

1310730

Hom.:

618

Cov.:

AF XY:

0.0123

AC XY:

8102

AN XY:

660338

show subpopulations

African (AFR)

AF:

0.135

AC:

4099

AN:

30316

American (AMR)

AF:

0.0228

AC:

1016

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.000832

AC:

AN:

25246

East Asian (EAS)

AF:

0.102

AC:

3966

AN:

38968

South Asian (SAS)

AF:

0.0195

AC:

1627

AN:

83410

European-Finnish (FIN)

AF:

0.00130

AC:

AN:

52918

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.00480

AC:

4682

AN:

974438

Other (OTH)

AF:

0.0186

AC:

1032

AN:

55426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

908

1817

2725

3634

4542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.0441

AC:

6717

AN:

152286

Hom.:

399

Cov.:

AF XY:

0.0437

AC XY:

3250

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.129

AC:

5363

AN:

41554

American (AMR)

AF:

0.0282

AC:

432

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.0877

AC:

451

AN:

5144

South Asian (SAS)

AF:

0.0230

AC:

111

AN:

4828

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00400

AC:

272

AN:

68038

Other (OTH)

AF:

0.0340

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

289

579

868

1158

1447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0406

Hom.:

304

Bravo

AF:

0.0502

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 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. -

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

-0.87

CADD

Benign

0.21

(source)

DANN

Benign

0.78

PhyloP100

0.78

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