chr6-70241400-A-G

Position:

• chr6-70241400-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.2034+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,597,660 control chromosomes in the GnomAD database, including 28,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2016 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26660 hom.)
• Consequence: COL9A1 NM_001851.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.908

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]

COL9A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-70241400-A-G is Benign according to our data. Variant chr6-70241400-A-G is described in ClinVar as [Benign]. Clinvar id is 258354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-70241400-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A1	NM_001851.6	c.2034+19T>C		intron_variant		ENST00000357250.11	NP_001842.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11	c.2034+19T>C		intron_variant		1	NM_001851.6	ENSP00000349790.6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22405 AN: 152136 Hom.: 2016 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.150 AC: 37617 AN: 251336 Hom.: 3489 AF XY: 0.153 AC XY: 20740 AN XY: 135854

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.0867

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0777

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.184 AC: 265252 AN: 1445406 Hom.: 26660 Cov.: 28 AF XY: 0.181 AC XY: 130686 AN XY: 720234

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.0901

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.000656

Gnomad4 SAS exome AF: 0.0804

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.147 AC: 22405 AN: 152254 Hom.: 2016 Cov.: 32 AF XY: 0.145 AC XY: 10801 AN XY: 74438

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.148

Alfa AF: 0.140 Hom.: 450

Bravo AF: 0.140

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 18, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.55

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: rs13202029; hg19: chr6-70951103;