chr6-70279648-CAAAAAA-C

Variant names:

• chr6-70279648-CAAAAAA-C
• rs57993118
• NM_001851.6:c.975+1158_975+1163delTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001851.6(COL9A1):​c.975+1158_975+1163delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 58,246 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 20)
  • Exomes 𝑓: 0.015 (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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00261 (150/57572) while in subpopulation NFE AF= 0.00435 (125/28722). AF 95% confidence interval is 0.00373. There are 1 homozygotes in gnomad4. There are 68 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+1158_975+1163delTTTTTT		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+1158_975+1163delTTTTTT		intron_variant	Intron 10 of 37	1	NM_001851.6	ENSP00000349790.6

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 150 AN: 57544 Hom.: 1 Cov.: 20

Gnomad AFR AF: 0.000671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00633

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00435

Gnomad OTH AF: 0.00141

GnomAD4 exome AF: 0.0148 AC: 10 AN: 674 Hom.: 0 AF XY: 0.0161 AC XY: 6 AN XY: 372

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.0417

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.0136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00261 AC: 150 AN: 57572 Hom.: 1 Cov.: 20 AF XY: 0.00257 AC XY: 68 AN XY: 26416

Gnomad4 AFR AF: 0.000669

Gnomad4 AMR AF: 0.000642

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00633

Gnomad4 NFE AF: 0.00435

Gnomad4 OTH AF: 0.00140

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;