chr9-134825764-T-C

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.4955-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,488,796 control chromosomes in the GnomAD database, including 374,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38841 hom., cov: 33)

Exomes 𝑓: 0.71 ( 335731 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.28

Publications

8 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:

LOC101448202 (HGNC:):

LOC101448202 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=-0.9).

BP6

Variant 9-134825764-T-C is Benign according to our data. Variant chr9-134825764-T-C is described in ClinVar as Benign. ClinVar VariationId is 255092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL5A1	NM_000093.5	MANE Select	c.4955-28T>C	intron	N/A	NP_000084.3
COL5A1	NM_001278074.1		c.4955-28T>C	intron	N/A	NP_001265003.1	P20908-2
LOC101448202	NR_103451.2		n.71-5555A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.4955-28T>C	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.4955-28T>C	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.4946-28T>C	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108617

AN:

152074

Hom.:

38816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.674

Gnomad ASJ

AF:

0.785

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.710

GnomAD2 exomes

AF:

0.720

AC:

179176

AN:

248800

AF XY:

0.726

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.661

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.721

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.712

GnomAD4 exome

AF:

0.708

AC:

945974

AN:

1336604

Hom.:

335731

Cov.:

AF XY:

0.710

AC XY:

477090

AN XY:

671614

show subpopulations

African (AFR)

AF:

0.736

AC:

22786

AN:

30954

American (AMR)

AF:

0.665

AC:

29368

AN:

44176

Ashkenazi Jewish (ASJ)

AF:

0.785

AC:

19783

AN:

25206

East Asian (EAS)

AF:

0.732

AC:

28413

AN:

38812

South Asian (SAS)

AF:

0.790

AC:

65741

AN:

83266

European-Finnish (FIN)

AF:

0.719

AC:

37851

AN:

52676

Middle Eastern (MID)

AF:

0.754

AC:

4144

AN:

5498

European-Non Finnish (NFE)

AF:

0.698

AC:

697902

AN:

999982

Other (OTH)

AF:

0.714

AC:

39986

AN:

56034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

12157

24314

36470

48627

60784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17078

34156

51234

68312

85390

<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:

0.714

AC:

108690

AN:

152192

Hom.:

38841

Cov.:

AF XY:

0.718

AC XY:

53389

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.729

AC:

30268

AN:

41520

American (AMR)

AF:

0.675

AC:

10322

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.785

AC:

2725

AN:

3470

East Asian (EAS)

AF:

0.763

AC:

3948

AN:

5174

South Asian (SAS)

AF:

0.807

AC:

3895

AN:

4826

European-Finnish (FIN)

AF:

0.723

AC:

7655

AN:

10592

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.697

AC:

47372

AN:

67994

Other (OTH)

AF:

0.709

AC:

1498

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1653

3305

4958

6610

8263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.666

Hom.:

4084

Bravo

AF:

0.715

Asia WGS

AF:

0.786

AC:

2729

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

-0.90

CADD

Benign

0.37

(source)

DANN

Benign

0.35

PhyloP100

-4.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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