chr9-134810351-G-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.3528+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 1,601,092 control chromosomes in the GnomAD database, including 2,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 145 hom., cov: 34)

Exomes 𝑓: 0.049 ( 1890 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.991

Publications

1 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=-0.93).

BP6

Variant 9-134810351-G-A is Benign according to our data. Variant chr9-134810351-G-A is described in ClinVar as Benign. ClinVar VariationId is 255080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0557 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.3528+43G>A		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.3528+43G>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.3528+43G>A	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.3528+43G>A	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.3519+43G>A	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5830

AN:

152206

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00936

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0739

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0572

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0409

AC:

10148

AN:

247966

AF XY:

0.0411

show subpopulations

Gnomad AFR exome

AF:

0.00817

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0393

Gnomad EAS exome

AF:

0.000440

Gnomad FIN exome

AF:

0.0708

Gnomad NFE exome

AF:

0.0592

Gnomad OTH exome

AF:

0.0468

GnomAD4 exome

AF:

0.0490

AC:

71047

AN:

1448768

Hom.:

1890

Cov.:

AF XY:

0.0482

AC XY:

34766

AN XY:

720630

show subpopulations

African (AFR)

AF:

0.00790

AC:

262

AN:

33174

American (AMR)

AF:

0.0204

AC:

910

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.0387

AC:

1006

AN:

25998

East Asian (EAS)

AF:

0.000304

AC:

AN:

39538

South Asian (SAS)

AF:

0.0171

AC:

1466

AN:

85900

European-Finnish (FIN)

AF:

0.0707

AC:

3767

AN:

53290

Middle Eastern (MID)

AF:

0.0347

AC:

197

AN:

5682

European-Non Finnish (NFE)

AF:

0.0552

AC:

60807

AN:

1100800

Other (OTH)

AF:

0.0438

AC:

2620

AN:

59880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3203

6406

9609

12812

16015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2172

4344

6516

8688

10860

<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:

0.0383

AC:

5830

AN:

152324

Hom.:

145

Cov.:

AF XY:

0.0380

AC XY:

2830

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00933

AC:

388

AN:

41588

American (AMR)

AF:

0.0268

AC:

411

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0444

AC:

154

AN:

3470

East Asian (EAS)

AF:

0.000773

AC:

AN:

5172

South Asian (SAS)

AF:

0.0174

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0739

AC:

784

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0572

AC:

3891

AN:

68026

Other (OTH)

AF:

0.0341

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

314

629

943

1258

1572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0454

Hom.:

Bravo

AF:

0.0344

Asia WGS

AF:

0.0150

AC:

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

-0.93

CADD

Benign

0.0070

(source)

DANN

Benign

0.70

PhyloP100

-0.99

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over