rs45629034

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.3745-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,611,018 control chromosomes in the GnomAD database, including 7,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1015 hom., cov: 33)

Exomes 𝑓: 0.090 ( 6300 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.10

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: Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
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=-0.99).

BP6

Variant 9-134812568-G-A is Benign according to our data. Variant chr9-134812568-G-A is described in ClinVar as Benign. ClinVar VariationId is 255082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.3745-37G>A		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.3745-37G>A		intron	N/A	NP_001265003.1	P20908-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.3745-37G>A	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.3745-37G>A	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.3736-37G>A	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16093

AN:

152080

Hom.:

1011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0605

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0369

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0849

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.0876

Gnomad OTH

AF:

0.0989

GnomAD2 exomes

AF:

0.0868

AC:

21569

AN:

248518

AF XY:

0.0879

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.0433

Gnomad ASJ exome

AF:

0.0997

Gnomad EAS exome

AF:

0.0363

Gnomad FIN exome

AF:

0.0910

Gnomad NFE exome

AF:

0.0904

Gnomad OTH exome

AF:

0.0891

GnomAD4 exome

AF:

0.0904

AC:

131824

AN:

1458820

Hom.:

6300

Cov.:

AF XY:

0.0904

AC XY:

65590

AN XY:

725828

show subpopulations

African (AFR)

AF:

0.173

AC:

5799

AN:

33436

American (AMR)

AF:

0.0461

AC:

2059

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

2658

AN:

26104

East Asian (EAS)

AF:

0.0528

AC:

2094

AN:

39692

South Asian (SAS)

AF:

0.0974

AC:

8389

AN:

86092

European-Finnish (FIN)

AF:

0.0894

AC:

4766

AN:

53328

Middle Eastern (MID)

AF:

0.111

AC:

642

AN:

5762

European-Non Finnish (NFE)

AF:

0.0900

AC:

99865

AN:

1109504

Other (OTH)

AF:

0.0921

AC:

5552

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

6435

12871

19306

25742

32177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3748

7496

11244

14992

18740

<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:

0.106

AC:

16113

AN:

152198

Hom.:

1015

Cov.:

AF XY:

0.103

AC XY:

7696

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.168

AC:

6978

AN:

41510

American (AMR)

AF:

0.0604

AC:

925

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

355

AN:

3470

East Asian (EAS)

AF:

0.0372

AC:

192

AN:

5158

South Asian (SAS)

AF:

0.102

AC:

491

AN:

4822

European-Finnish (FIN)

AF:

0.0849

AC:

900

AN:

10602

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0875

AC:

5954

AN:

68014

Other (OTH)

AF:

0.103

AC:

217

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

740

1479

2219

2958

3698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0942

Hom.:

135

Bravo

AF:

0.105

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Ehlers-Danlos syndrome, classic type, 1 (1)

Fibromuscular dysplasia, multifocal (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.082

(source)

DANN

Benign

0.73

PhyloP100

-5.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over