rs2242588

chr6-70302872-T-Cchr6-70302872-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001851.6(COL9A1):c.14+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,608,776 control chromosomes in the GnomAD database, including 28,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4054 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24814 hom.)
• Consequence: COL9A1 NM_001851.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0840

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-70302872-T-C is Benign according to our data. Variant chr6-70302872-T-C is described in ClinVar as [Benign]. Clinvar id is 258342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A1	NM_001851.6	c.14+39A>G		intron_variant		ENST00000357250.11
COL9A1	NM_001377291.1	c.14+39A>G		intron_variant
COL9A1	XM_011535429.4	c.14+39A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11	c.14+39A>G		intron_variant		1	NM_001851.6	P1
COL9A1	ENST00000370496.3	c.14+39A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32756 AN: 151764 Hom.: 4033 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.186 AC: 46808 AN: 251414 Hom.: 4760 AF XY: 0.184 AC XY: 25010 AN XY: 135878

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.172

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.181 AC: 263509 AN: 1456894 Hom.: 24814 Cov.: 30 AF XY: 0.182 AC XY: 132174 AN XY: 725052

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.216 AC: 32820 AN: 151882 Hom.: 4054 Cov.: 31 AF XY: 0.213 AC XY: 15787 AN XY: 74252

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.195

Alfa AF: 0.177 Hom.: 2725

Bravo AF: 0.220

Asia WGS AF: 0.227 AC: 793 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.4
Dann	Benign	0.75

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: rs2242588; hg19: chr6-71012575;