rs41298367

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000093.5(COL5A1):c.2034+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,609,602 control chromosomes in the GnomAD database, including 673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 36 hom., cov: 32)

Exomes 𝑓: 0.026 ( 637 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.71

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: 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:

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=-0.97).

BP6

Variant 9-134763761-C-T is Benign according to our data. Variant chr9-134763761-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0198 (3007/152102) while in subpopulation NFE AF = 0.0296 (2011/67976). AF 95% confidence interval is 0.0285. There are 36 homozygotes in GnomAd4. There are 1437 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3007 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.2034+24C>T	intron_variant	Intron 20 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.2034+24C>T	intron_variant	Intron 20 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.2034+24C>T	intron_variant	Intron 20 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2034+24C>T		intron_variant	Intron 20 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.2034+24C>T		intron_variant	Intron 20 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3008

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00570

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.0414

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0194

AC:

4860

AN:

250158

AF XY:

0.0192

show subpopulations

Gnomad AFR exome

AF:

0.00481

Gnomad AMR exome

AF:

0.00753

Gnomad ASJ exome

AF:

0.00950

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0359

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0264

AC:

38502

AN:

1457500

Hom.:

637

Cov.:

AF XY:

0.0256

AC XY:

18544

AN XY:

725256

show subpopulations

African (AFR)

AF:

0.00404

AC:

135

AN:

33422

American (AMR)

AF:

0.00833

AC:

372

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00874

AC:

228

AN:

26084

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39668

South Asian (SAS)

AF:

0.00556

AC:

479

AN:

86140

European-Finnish (FIN)

AF:

0.0352

AC:

1873

AN:

53174

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0307

AC:

34077

AN:

1108388

Other (OTH)

AF:

0.0219

AC:

1317

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

1574

3149

4723

6298

7872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1262

2524

3786

5048

6310

<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:

0.0198

AC:

3007

AN:

152102

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1437

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00569

AC:

236

AN:

41506

American (AMR)

AF:

0.0146

AC:

224

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.00457

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0414

AC:

439

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0296

AC:

2011

AN:

67976

Other (OTH)

AF:

0.0137

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

152

304

457

609

761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0216

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Likely 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

-0.97

CADD

Benign

0.0030

(source)

DANN

Benign

0.77

PhyloP100

-4.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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