9-134767390-C-T

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.2232+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,598,972 control chromosomes in the GnomAD database, including 582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 46 hom., cov: 33)

Exomes 𝑓: 0.026 ( 536 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0170

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=-0.89).

BP6

Variant 9-134767390-C-T is Benign according to our data. Variant chr9-134767390-C-T is described in ClinVar as Benign. ClinVar VariationId is 255061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0249 (3794/152258) while in subpopulation EAS AF = 0.0529 (273/5164). AF 95% confidence interval is 0.0477. There are 46 homozygotes in GnomAd4. There are 1868 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3794 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COL5A1	NM_000093.5 link	c.2232+36C>T	intron_variant	Intron 24 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 link	c.2232+36C>T	intron_variant	Intron 24 of 65		NP_001265003.1
COL5A1	XM_017014266.3 link	c.2232+36C>T	intron_variant	Intron 24 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2232+36C>T		intron_variant	Intron 24 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4 link	c.2232+36C>T		intron_variant	Intron 24 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3793

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.0321

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0264

AC:

6599

AN:

249828

AF XY:

0.0265

show subpopulations

Gnomad AFR exome

AF:

0.0235

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.0568

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0256

AC:

36994

AN:

1446714

Hom.:

536

Cov.:

AF XY:

0.0256

AC XY:

18426

AN XY:

720464

show subpopulations

African (AFR)

AF:

0.0209

AC:

693

AN:

33142

American (AMR)

AF:

0.0184

AC:

823

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

509

AN:

26054

East Asian (EAS)

AF:

0.0399

AC:

1583

AN:

39626

South Asian (SAS)

AF:

0.0244

AC:

2100

AN:

85964

European-Finnish (FIN)

AF:

0.0294

AC:

1559

AN:

53020

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

0.0254

AC:

27952

AN:

1098798

Other (OTH)

AF:

0.0286

AC:

1715

AN:

59900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1812

3624

5435

7247

9059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1042

2084

3126

4168

5210

<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:

0.0249

AC:

3794

AN:

152258

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1868

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0218

AC:

905

AN:

41550

American (AMR)

AF:

0.0181

AC:

277

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.0529

AC:

273

AN:

5164

South Asian (SAS)

AF:

0.0238

AC:

115

AN:

4826

European-Finnish (FIN)

AF:

0.0321

AC:

341

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0258

AC:

1757

AN:

68016

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

195

390

585

780

975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0264

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.0390

AC:

137

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

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.89

CADD

Benign

2.3

(source)

DANN

Benign

0.37

PhyloP100

0.017

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