chr6-70279648-C-CAA

Variant names:

• chr6-70279648-C-CAA
• rs57993118
• NM_001851.6:c.975+1162_975+1163dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001851.6(COL9A1):​c.975+1162_975+1163dupTT 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 0.0061 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0074 (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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00614 (340/55380) while in subpopulation NFE AF= 0.00866 (234/27020). AF 95% confidence interval is 0.00775. There are 0 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6	c.975+1162_975+1163dupTT		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+1164insTT		intron_variant	Intron 10 of 37	1	NM_001851.6	ENSP00000349790.6

Frequencies

GnomAD3 genomes AF: 0.00614 AC: 340 AN: 55352 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.00352

Gnomad ASJ AF: 0.00714

Gnomad EAS AF: 0.00335

Gnomad SAS AF: 0.00772

Gnomad FIN AF: 0.00193

Gnomad MID AF: 0.0270

Gnomad NFE AF: 0.00866

Gnomad OTH AF: 0.00436

GnomAD4 exome AF: 0.00742 AC: 5 AN: 674 Hom.: 0 Cov.: 0 AF XY: 0.00541 AC XY: 2 AN XY: 370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00909

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00614 AC: 340 AN: 55380 Hom.: 0 Cov.: 20 AF XY: 0.00659 AC XY: 168 AN XY: 25508

Gnomad4 AFR AF: 0.00319

Gnomad4 AMR AF: 0.00351

Gnomad4 ASJ AF: 0.00714

Gnomad4 EAS AF: 0.00336

Gnomad4 SAS AF: 0.00774

Gnomad4 FIN AF: 0.00193

Gnomad4 NFE AF: 0.00866

Gnomad4 OTH AF: 0.00432

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;