6-70216654-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001851.6(COL9A1):c.*242_*243insAA 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 0.086 (719 hom., cov: 0)
  • Exomes 𝑓: 0.039 (37 hom.)
• Consequence: COL9A1 NM_001851.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-70216654-C-CTT is Benign according to our data. Variant chr6-70216654-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1259219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A1	NM_001851.6	c.*242_*243insAA		3_prime_UTR_variant	38/38	ENST00000357250.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11	c.*242_*243insAA		3_prime_UTR_variant	38/38	1	NM_001851.6	P1

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 12578 AN: 145788 Hom.: 719 Cov.: 0

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0201

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0425

Gnomad EAS AF: 0.00523

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0201

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0696

GnomAD4 exome AF: 0.0391 AC: 13084 AN: 334820 Hom.: 37 Cov.: 0 AF XY: 0.0384 AC XY: 6753 AN XY: 176066

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.00791

Gnomad4 SAS exome AF: 0.0344

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.0407

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0863 AC: 12580 AN: 145828 Hom.: 719 Cov.: 0 AF XY: 0.0852 AC XY: 6036 AN XY: 70814

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0425

Gnomad4 EAS AF: 0.00524

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0607

Gnomad4 OTH AF: 0.0692

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215859; hg19: chr6-70926357;