rs2294988

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001853.4(COL9A3):c.477+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,332,424 control chromosomes in the GnomAD database, including 67,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6186 hom., cov: 32)

Exomes 𝑓: 0.32 ( 60969 hom. )

Consequence

COL9A3
NM_001853.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.12

Publications

12 publications found

Variant links:

Genes affected

COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]

COL9A3 Gene-Disease associations (from GenCC):

epiphyseal dysplasia, multiple, 3
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
Stickler syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen
Stickler syndrome, type 6
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple epiphyseal dysplasia due to collagen 9 anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Stickler syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL9A3 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=-0.84).

BP6

Variant 20-62822197-G-A is Benign according to our data. Variant chr20-62822197-G-A is described in ClinVar as Benign. ClinVar VariationId is 258425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.477+33G>A		intron_variant	Intron 9 of 31	ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL9A3	ENST00000649368.1 link	c.477+33G>A	intron_variant	Intron 9 of 31		NM_001853.4	ENSP00000496793.1
COL9A3	ENST00000452372.2 link	c.366+33G>A	intron_variant	Intron 8 of 11	5		ENSP00000394280.1
COL9A3	ENST00000477612.5 link	n.473+33G>A	intron_variant	Intron 9 of 11	3
COL9A3	ENST00000489045.5 link	n.523+33G>A	intron_variant	Intron 8 of 13	5

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41888

AN:

151962

Hom.:

6186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.300

AC:

74420

AN:

248048

AF XY:

0.299

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.319

AC:

376466

AN:

1180346

Hom.:

60969

Cov.:

AF XY:

0.317

AC XY:

190175

AN XY:

600194

show subpopulations

African (AFR)

AF:

0.179

AC:

5034

AN:

28096

American (AMR)

AF:

0.304

AC:

13503

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

6692

AN:

24338

East Asian (EAS)

AF:

0.241

AC:

9300

AN:

38524

South Asian (SAS)

AF:

0.258

AC:

20804

AN:

80712

European-Finnish (FIN)

AF:

0.360

AC:

18787

AN:

52184

Middle Eastern (MID)

AF:

0.282

AC:

1481

AN:

5248

European-Non Finnish (NFE)

AF:

0.333

AC:

285239

AN:

855766

Other (OTH)

AF:

0.306

AC:

15626

AN:

51124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11246

22491

33737

44982

56228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8214

16428

24642

32856

41070

<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:

0.276

AC:

41905

AN:

152078

Hom.:

6186

Cov.:

AF XY:

0.276

AC XY:

20539

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.181

AC:

7505

AN:

41496

American (AMR)

AF:

0.283

AC:

4329

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

957

AN:

3468

East Asian (EAS)

AF:

0.240

AC:

1237

AN:

5160

South Asian (SAS)

AF:

0.250

AC:

1205

AN:

4814

European-Finnish (FIN)

AF:

0.363

AC:

3849

AN:

10590

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21972

AN:

67954

Other (OTH)

AF:

0.279

AC:

588

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1533

3066

4600

6133

7666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.307

Hom.:

9821

Bravo

AF:

0.268

Asia WGS

AF:

0.251

AC:

875

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.10

(source)

DANN

Benign

0.68

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over