9-134738722-C-T

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.1432-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,595,100 control chromosomes in the GnomAD database, including 212,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.56 ( 25568 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186627 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.644

Publications

12 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-134738722-C-T is Benign according to our data. Variant chr9-134738722-C-T is described in ClinVar as Benign. ClinVar VariationId is 255050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 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.1432-24C>T		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.1432-24C>T		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.1432-24C>T	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.1432-24C>T	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.1423-24C>T	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85467

AN:

151810

Hom.:

25539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.480

AC:

120013

AN:

250028

AF XY:

0.481

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.503

AC:

725521

AN:

1443172

Hom.:

186627

Cov.:

AF XY:

0.502

AC XY:

360654

AN XY:

719010

show subpopulations

African (AFR)

AF:

0.788

AC:

25953

AN:

32920

American (AMR)

AF:

0.266

AC:

11875

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

8486

AN:

26022

East Asian (EAS)

AF:

0.518

AC:

20500

AN:

39544

South Asian (SAS)

AF:

0.483

AC:

41470

AN:

85822

European-Finnish (FIN)

AF:

0.506

AC:

26950

AN:

53312

Middle Eastern (MID)

AF:

0.450

AC:

2578

AN:

5730

European-Non Finnish (NFE)

AF:

0.509

AC:

557859

AN:

1095354

Other (OTH)

AF:

0.499

AC:

29850

AN:

59848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

16345

32690

49036

65381

81726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16020

32040

48060

64080

80100

<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:

0.563

AC:

85542

AN:

151928

Hom.:

25568

Cov.:

AF XY:

0.555

AC XY:

41217

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.774

AC:

32038

AN:

41406

American (AMR)

AF:

0.371

AC:

5669

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1170

AN:

3468

East Asian (EAS)

AF:

0.504

AC:

2579

AN:

5122

South Asian (SAS)

AF:

0.482

AC:

2321

AN:

4812

European-Finnish (FIN)

AF:

0.503

AC:

5322

AN:

10582

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.511

AC:

34678

AN:

67922

Other (OTH)

AF:

0.497

AC:

1050

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1804

3609

5413

7218

9022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.520

Hom.:

48051

Bravo

AF:

0.562

Asia WGS

AF:

0.467

AC:

1629

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

-0.89

CADD

Benign

0.82

(source)

DANN

Benign

0.38

PhyloP100

-0.64

BranchPoint Hunter

1.0

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.

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