NM_000093.5:c.925-43G>A

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.925-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,605,376 control chromosomes in the GnomAD database, including 162,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13278 hom., cov: 34)

Exomes 𝑓: 0.45 ( 148858 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.73

Publications

6 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 9-134730193-G-A is Benign according to our data. Variant chr9-134730193-G-A is described in ClinVar as [Benign]. Clinvar id is 255101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.925-43G>A	intron_variant	Intron 6 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.925-43G>A	intron_variant	Intron 6 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.925-43G>A	intron_variant	Intron 6 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.925-43G>A		intron_variant	Intron 6 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.925-43G>A		intron_variant	Intron 6 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60611

AN:

151732

Hom.:

13261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.450

GnomAD2 exomes

AF:

0.478

AC:

117329

AN:

245350

AF XY:

0.475

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.707

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.441

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.447

AC:

649937

AN:

1453526

Hom.:

148858

Cov.:

AF XY:

0.448

AC XY:

324079

AN XY:

723354

show subpopulations

African (AFR)

AF:

0.207

AC:

6911

AN:

33412

American (AMR)

AF:

0.693

AC:

30973

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

16304

AN:

26112

East Asian (EAS)

AF:

0.471

AC:

18686

AN:

39682

South Asian (SAS)

AF:

0.468

AC:

40321

AN:

86138

European-Finnish (FIN)

AF:

0.462

AC:

22490

AN:

48654

Middle Eastern (MID)

AF:

0.497

AC:

2580

AN:

5196

European-Non Finnish (NFE)

AF:

0.437

AC:

484408

AN:

1109484

Other (OTH)

AF:

0.453

AC:

27264

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

17889

35777

53666

71554

89443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.399

AC:

60663

AN:

151850

Hom.:

13278

Cov.:

AF XY:

0.407

AC XY:

30225

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.221

AC:

9155

AN:

41496

American (AMR)

AF:

0.574

AC:

8751

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2143

AN:

3460

East Asian (EAS)

AF:

0.480

AC:

2461

AN:

5130

South Asian (SAS)

AF:

0.463

AC:

2232

AN:

4818

European-Finnish (FIN)

AF:

0.461

AC:

4850

AN:

10532

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.437

AC:

29681

AN:

67864

Other (OTH)

AF:

0.453

AC:

958

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1811

3623

5434

7246

9057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.433

Hom.:

2866

Bravo

AF:

0.402

Asia WGS

AF:

0.506

AC:

1756

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 14, 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

-0.97

CADD

Benign

0.10

(source)

DANN

Benign

0.65

PhyloP100

-2.7

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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NM_000093.5:c.925-43G>A

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