rs607156

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001851.6(COL9A1):c.1071T>C(p.Arg357Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,611,098 control chromosomes in the GnomAD database, including 2,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 899 hom., cov: 32)

Exomes 𝑓: 0.025 ( 1507 hom. )

Consequence

COL9A1
NM_001851.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.02

Publications

11 publications found

Variant links:

Genes affected

COL9A1 (HGNC:2217): (collagen type IX alpha 1 chain) This gene encodes one of the three alpha chains of type IX collagen, which is a minor (5-20%) collagen component of hyaline cartilage. Type IX collagen is usually found in tissues containing type II collagen, a fibrillar collagen. Studies in knockout mice have shown that synthesis of the alpha 1 chain is essential for assembly of type IX collagen molecules, a heterotrimeric molecule, and that lack of type IX collagen is associated with early onset osteoarthritis. Mutations in this gene are associated with osteoarthritis in humans, with multiple epiphyseal dysplasia, 6, a form of chondrodysplasia, and with Stickler syndrome, a disease characterized by ophthalmic, orofacial, articular, and auditory defects. Two transcript variants that encode different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

COL9A1 Gene-Disease associations (from GenCC):

epiphyseal dysplasia, multiple, 6
Inheritance: AD, AR, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Stickler syndrome, type 4
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, PanelApp Australia, 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
Stickler syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

COL9A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 6-70272083-A-G is Benign according to our data. Variant chr6-70272083-A-G is described in ClinVar as Benign. ClinVar VariationId is 258338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6 link	c.1071T>C	p.Arg357Arg	synonymous_variant	Exon 13 of 38	ENST00000357250.11	NP_001842.3	P20849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11 link	c.1071T>C	p.Arg357Arg	synonymous_variant	Exon 13 of 38	1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.0719

AC:

10929

AN:

152062

Hom.:

893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0697

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0580

GnomAD2 exomes

AF:

0.0452

AC:

11290

AN:

249980

AF XY:

0.0410

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.0656

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.00426

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0313

GnomAD4 exome

AF:

0.0249

AC:

36266

AN:

1458918

Hom.:

1507

Cov.:

AF XY:

0.0247

AC XY:

17937

AN XY:

725898

show subpopulations

African (AFR)

AF:

0.194

AC:

6462

AN:

33270

American (AMR)

AF:

0.0634

AC:

2831

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00364

AC:

AN:

26104

East Asian (EAS)

AF:

0.158

AC:

6244

AN:

39598

South Asian (SAS)

AF:

0.0449

AC:

3862

AN:

86034

European-Finnish (FIN)

AF:

0.00459

AC:

245

AN:

53378

Middle Eastern (MID)

AF:

0.0341

AC:

196

AN:

5754

European-Non Finnish (NFE)

AF:

0.0127

AC:

14127

AN:

1109874

Other (OTH)

AF:

0.0366

AC:

2204

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

1519

3038

4556

6075

7594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.0721

AC:

10974

AN:

152180

Hom.:

899

Cov.:

AF XY:

0.0719

AC XY:

5347

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.188

AC:

7816

AN:

41474

American (AMR)

AF:

0.0697

AC:

1066

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3468

East Asian (EAS)

AF:

0.154

AC:

800

AN:

5182

South Asian (SAS)

AF:

0.0433

AC:

209

AN:

4822

European-Finnish (FIN)

AF:

0.00481

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

878

AN:

68010

Other (OTH)

AF:

0.0611

AC:

129

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

452

905

1357

1810

2262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0381

Hom.:

309

Bravo

AF:

0.0829

Asia WGS

AF:

0.114

AC:

395

AN:

3478

EpiCase

AF:

0.0137

EpiControl

AF:

0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 17, 2016

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 24, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.46

CADD

Benign

8.3

(source)

DANN

Benign

0.77

PhyloP100

2.0

Mutation Taster

=94/6

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over