9-134817127-A-G

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.4176+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,550,680 control chromosomes in the GnomAD database, including 138,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17322 hom., cov: 33)

Exomes 𝑓: 0.41 ( 121280 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.27

Publications

7 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=-0.91).

BP6

Variant 9-134817127-A-G is Benign according to our data. Variant chr9-134817127-A-G is described in ClinVar as [Benign]. Clinvar id is 255086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4176+48A>G	intron_variant	Intron 53 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.4176+48A>G	intron_variant	Intron 53 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4176+48A>G	intron_variant	Intron 53 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.4176+48A>G		intron_variant	Intron 53 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.4176+48A>G		intron_variant	Intron 53 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70824

AN:

151782

Hom.:

17296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.452

GnomAD2 exomes

AF:

0.416

AC:

102242

AN:

246056

AF XY:

0.409

show subpopulations

Gnomad AFR exome

AF:

0.631

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.414

AC:

578778

AN:

1398780

Hom.:

121280

Cov.:

AF XY:

0.412

AC XY:

288278

AN XY:

699394

show subpopulations

African (AFR)

AF:

0.632

AC:

20540

AN:

32512

American (AMR)

AF:

0.375

AC:

16581

AN:

44196

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

9463

AN:

25656

East Asian (EAS)

AF:

0.451

AC:

17761

AN:

39340

South Asian (SAS)

AF:

0.352

AC:

29905

AN:

84924

European-Finnish (FIN)

AF:

0.360

AC:

19048

AN:

52872

Middle Eastern (MID)

AF:

0.441

AC:

2276

AN:

5164

European-Non Finnish (NFE)

AF:

0.416

AC:

438733

AN:

1055830

Other (OTH)

AF:

0.420

AC:

24471

AN:

58286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

14192

28384

42576

56768

70960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.467

AC:

70902

AN:

151900

Hom.:

17322

Cov.:

AF XY:

0.460

AC XY:

34126

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.622

AC:

25780

AN:

41414

American (AMR)

AF:

0.394

AC:

6017

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1265

AN:

3464

East Asian (EAS)

AF:

0.459

AC:

2364

AN:

5150

South Asian (SAS)

AF:

0.338

AC:

1625

AN:

4804

European-Finnish (FIN)

AF:

0.364

AC:

3848

AN:

10568

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28559

AN:

67908

Other (OTH)

AF:

0.450

AC:

952

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1929

3858

5787

7716

9645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.446

Hom.:

2869

Bravo

AF:

0.479

Asia WGS

AF:

0.401

AC:

1399

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 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.91

CADD

Benign

0.54

(source)

DANN

Benign

0.37

PhyloP100

-1.3

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.

9-134817127-A-G

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