6-70216654-C-CT

Variant names:

• chr6-70216654-C-CT
• rs3215859
• NM_001851.6:c.*242dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001851.6(COL9A1):​c.*242dupA 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.00
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
COL9A1	NM_001851.6	c.*242dupA		3_prime_UTR_variant	Exon 38 of 38	ENST00000357250.11	NP_001842.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11	c.*242dupA		3_prime_UTR_variant	Exon 38 of 38	1	NM_001851.6	ENSP00000349790.6

Frequencies

GnomAD3 genomes AF: 0.241 AC: 35140 AN: 145768 Hom.: 4746 Cov.: 0

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.: 0 AF XY: 0.221 AC XY: 38492 AN XY: 174402

African (AFR) AF: 0.130 AC: 1224 AN: 9412

American (AMR) AF: 0.283 AC: 4049 AN: 14322

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 1893 AN: 10194

East Asian (EAS) AF: 0.300 AC: 6594 AN: 22008

South Asian (SAS) AF: 0.185 AC: 6838 AN: 36966

European-Finnish (FIN) AF: 0.247 AC: 4800 AN: 19418

Middle Eastern (MID) AF: 0.201 AC: 291 AN: 1450

European-Non Finnish (NFE) AF: 0.223 AC: 44449 AN: 199296

Other (OTH) AF: 0.222 AC: 4179 AN: 18784

GnomAD4 genome AF: 0.241 AC: 35142 AN: 145806 Hom.: 4745 Cov.: 0 AF XY: 0.246 AC XY: 17412 AN XY: 70816

African (AFR) AF: 0.110 AC: 4348 AN: 39636

American (AMR) AF: 0.349 AC: 5162 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 722 AN: 3402

East Asian (EAS) AF: 0.433 AC: 2144 AN: 4954

South Asian (SAS) AF: 0.217 AC: 980 AN: 4526

European-Finnish (FIN) AF: 0.322 AC: 2928 AN: 9090

Middle Eastern (MID) AF: 0.250 AC: 68 AN: 272

European-Non Finnish (NFE) AF: 0.272 AC: 18001 AN: 66234

Other (OTH) AF: 0.244 AC: 494 AN: 2026

Alfa AF: 0.128 Hom.: 232

Bravo AF: 0.241

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Stickler Syndrome, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Multiple Epiphyseal Dysplasia, Dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3215859; hg19: chr6-70926357;