rs10776910

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.4176+35A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,593,238 control chromosomes in the GnomAD database, including 143,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17317 hom., cov: 33)

Exomes 𝑓: 0.42 ( 126586 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.10

Publications

9 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 9-134817114-A-C is Benign according to our data. Variant chr9-134817114-A-C is described in ClinVar as Benign. ClinVar VariationId is 255085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 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.4176+35A>C		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.4176+35A>C		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.4176+35A>C	intron	N/A	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4	TSL:2	c.4176+35A>C	intron	N/A	ENSP00000360885.4	P20908-2
COL5A1	ENST00000950240.1		c.4167+35A>C	intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70830

AN:

151884

Hom.:

17291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.453

GnomAD2 exomes

AF:

0.414

AC:

103242

AN:

249602

AF XY:

0.407

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.415

AC:

598688

AN:

1441236

Hom.:

126586

Cov.:

AF XY:

0.414

AC XY:

297030

AN XY:

718112

show subpopulations

African (AFR)

AF:

0.631

AC:

20984

AN:

33236

American (AMR)

AF:

0.374

AC:

16674

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

9603

AN:

25976

East Asian (EAS)

AF:

0.451

AC:

17854

AN:

39558

South Asian (SAS)

AF:

0.353

AC:

30263

AN:

85852

European-Finnish (FIN)

AF:

0.360

AC:

19117

AN:

53114

Middle Eastern (MID)

AF:

0.440

AC:

2413

AN:

5488

European-Non Finnish (NFE)

AF:

0.418

AC:

456636

AN:

1093680

Other (OTH)

AF:

0.421

AC:

25144

AN:

59728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

15312

30624

45936

61248

76560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13920

27840

41760

55680

69600

<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:

0.466

AC:

70908

AN:

152002

Hom.:

17317

Cov.:

AF XY:

0.459

AC XY:

34124

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.622

AC:

25780

AN:

41450

American (AMR)

AF:

0.394

AC:

6020

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1265

AN:

3464

East Asian (EAS)

AF:

0.458

AC:

2361

AN:

5154

South Asian (SAS)

AF:

0.337

AC:

1625

AN:

4818

European-Finnish (FIN)

AF:

0.364

AC:

3847

AN:

10564

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.420

AC:

28566

AN:

67950

Other (OTH)

AF:

0.451

AC:

952

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1942

3883

5825

7766

9708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.449

Hom.:

9580

Bravo

AF:

0.479

Asia WGS

AF:

0.402

AC:

1400

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

0.41

(source)

DANN

Benign

0.40

PhyloP100

-3.1

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