rs12191701

chr6-70234762-A-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.2259+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,612,902 control chromosomes in the GnomAD database, including 176,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (12012 hom., cov: 32)
  • Exomes 𝑓: 0.46 (164364 hom.)
• Consequence: COL9A1 NM_001851.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.556

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-70234762-A-G is Benign according to our data. Variant chr6-70234762-A-G is described in ClinVar as [Benign]. Clinvar id is 258357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A1	NM_001851.6	c.2259+32T>C		intron_variant		ENST00000357250.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11	c.2259+32T>C		intron_variant		1	NM_001851.6	P1
	ENST00000522264.1	n.82-7222A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54784 AN: 151992 Hom.: 12009 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.0381

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.377 AC: 94028 AN: 249132 Hom.: 21260 AF XY: 0.388 AC XY: 52291 AN XY: 134656

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.571

Gnomad EAS exome AF: 0.0367

Gnomad SAS exome AF: 0.300

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.460 AC: 672478 AN: 1460792 Hom.: 164364 Cov.: 45 AF XY: 0.457 AC XY: 332434 AN XY: 726634

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.0351

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.360 AC: 54778 AN: 152110 Hom.: 12012 Cov.: 32 AF XY: 0.354 AC XY: 26329 AN XY: 74352

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.369

Alfa AF: 0.473 Hom.: 23544

Bravo AF: 0.339

Asia WGS AF: 0.144 AC: 504 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

-

- -

Epiphyseal dysplasia, multiple, 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.9
Dann	Benign	0.62

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: rs12191701; hg19: chr6-70944465;