Variant 6-70216654-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001851.6(COL9A1):c.*242_*243insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4745 hom., cov: 0)

Exomes 𝑓: 0.22 ( 249 hom. )

Consequence

COL9A1
NM_001851.6 3_prime_UTR

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -2.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 6-70216654-C-CT is Benign according to our data. Variant chr6-70216654-C-CT is described in ClinVar as [Benign]. Clinvar id is 357793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A1	NM_001851.6 linkuse as main transcript	c.242_243insA		3_prime_UTR_variant	38/38	ENST00000357250.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11 linkuse as main transcript	c.242_243insA		3_prime_UTR_variant	38/38	1	NM_001851.6	P1	P20849-1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

35140

AN:

145768

Hom.:

4746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.247

GnomAD4 exome

AF:

0.224

AC:

74317

AN:

331850

Hom.:

249

Cov.:

AF XY:

0.221

AC XY:

38492

AN XY:

174402

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.241

AC:

35142

AN:

145806

Hom.:

4745

Cov.:

AF XY:

0.246

AC XY:

17412

AN XY:

70816

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.244

Bravo

AF:

0.241

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Stickler Syndrome, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

Multiple Epiphyseal Dysplasia, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over