rs117215769

chr6-70281377-G-A

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.876+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,610,872 control chromosomes in the GnomAD database, including 3,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (227 hom., cov: 31)
  • Exomes 𝑓: 0.059 (2884 hom.)
• Consequence: COL9A1 NM_001851.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0920

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=-0.88).
• BP6: Variant 6-70281377-G-A is Benign according to our data. Variant chr6-70281377-G-A is described in ClinVar as [Benign]. Clinvar id is 258361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-70281377-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A1	NM_001851.6	c.876+13C>T		intron_variant		ENST00000357250.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11	c.876+13C>T		intron_variant		1	NM_001851.6	P1

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6684 AN: 151406 Hom.: 227 Cov.: 31

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0373

Gnomad EAS AF: 0.00549

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0351

GnomAD3 exomes AF: 0.0456 AC: 11418 AN: 250370 Hom.: 354 AF XY: 0.0465 AC XY: 6302 AN XY: 135440

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0374

Gnomad EAS exome AF: 0.00409

Gnomad SAS exome AF: 0.0312

Gnomad FIN exome AF: 0.0624

Gnomad NFE exome AF: 0.0657

Gnomad OTH exome AF: 0.0471

GnomAD4 exome AF: 0.0589 AC: 85890 AN: 1459360 Hom.: 2884 Cov.: 31 AF XY: 0.0586 AC XY: 42516 AN XY: 726072

Gnomad4 AFR exome AF: 0.00897

Gnomad4 AMR exome AF: 0.0237

Gnomad4 ASJ exome AF: 0.0391

Gnomad4 EAS exome AF: 0.00209

Gnomad4 SAS exome AF: 0.0320

Gnomad4 FIN exome AF: 0.0648

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0492

GnomAD4 genome AF: 0.0441 AC: 6683 AN: 151512 Hom.: 227 Cov.: 31 AF XY: 0.0427 AC XY: 3159 AN XY: 74048

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0373

Gnomad4 EAS AF: 0.00550

Gnomad4 SAS AF: 0.0341

Gnomad4 FIN AF: 0.0557

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.0347

Alfa AF: 0.0599 Hom.: 81

Bravo AF: 0.0391

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.5
Dann	Benign	0.51

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: rs117215769; hg19: chr6-70991080;