chr6-70279648-C-CA

Variant names:

• chr6-70279648-C-CA
• rs57993118
• NM_001851.6:c.975+1163dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001851.6(COL9A1):​c.975+1163dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (63 hom., cov: 20)
  • Exomes 𝑓: 0.036 (0 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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0277 (1587/57260) while in subpopulation SAS AF= 0.0493 (64/1298). AF 95% confidence interval is 0.0396. There are 63 homozygotes in gnomad4. There are 764 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6	c.975+1163dupT		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+1163_975+1164insT		intron_variant	Intron 10 of 37	1	NM_001851.6	ENSP00000349790.6

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 1586 AN: 57232 Hom.: 63 Cov.: 20

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0395

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0257

GnomAD4 exome AF: 0.0356 AC: 24 AN: 674 Hom.: 0 Cov.: 0 AF XY: 0.0376 AC XY: 14 AN XY: 372

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0484

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0277 AC: 1587 AN: 57260 Hom.: 63 Cov.: 20 AF XY: 0.0291 AC XY: 764 AN XY: 26278

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.0493

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.0255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs57993118; hg19: chr6-70989351;