6-70279648-CAAAAAAAAAAAA-CAAAAAAA

Variant names:

• chr6-70279648-CAAAAA-C
• rs57993118
• NM_001851.6:c.975+1159_975+1163delTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001851.6(COL9A1):​c.975+1159_975+1163delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 58,284 control chromosomes in the GnomAD database, including 172 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.098 (170 hom., cov: 20)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: COL9A1 NM_001851.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6	c.975+1159_975+1163delTTTTT		intron_variant	Intron 10 of 37	ENST00000357250.11	NP_001842.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11	c.975+1159_975+1163delTTTTT		intron_variant	Intron 10 of 37	1	NM_001851.6	ENSP00000349790.6

Frequencies

GnomAD3 genomes AF: 0.0982 AC: 5654 AN: 57580 Hom.: 169 Cov.: 20

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0921

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0899

GnomAD4 exome AF: 0.107 AC: 72 AN: 676 Hom.: 2 AF XY: 0.0968 AC XY: 36 AN XY: 372

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0323

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0983 AC: 5663 AN: 57608 Hom.: 170 Cov.: 20 AF XY: 0.0947 AC XY: 2505 AN XY: 26446

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0117

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.0891

ClinVar

Not reported in ClinVar

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: rs57993118; hg19: chr6-70989351;