rs6935778

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001851.6(COL9A1):c.1230+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,569,944 control chromosomes in the GnomAD database, including 25,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2025 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23812 hom. )

Consequence

COL9A1
NM_001851.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.257

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 6-70269621-A-G is Benign according to our data. Variant chr6-70269621-A-G is described in ClinVar as [Benign]. Clinvar id is 258341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-70269621-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6 link	c.1230+12T>C		intron_variant	Intron 16 of 37	ENST00000357250.11	NP_001842.3	P20849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11 link	c.1230+12T>C		intron_variant	Intron 16 of 37	1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23515

AN:

152108

Hom.:

2026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0708

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.149

AC:

37200

AN:

250410

Hom.:

3372

AF XY:

0.151

AC XY:

20454

AN XY:

135448

show subpopulations

Gnomad AFR exome

AF:

0.0994

Gnomad AMR exome

AF:

0.0877

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0760

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.176

AC:

248821

AN:

1417718

Hom.:

23812

Cov.:

AF XY:

0.174

AC XY:

122970

AN XY:

708098

show subpopulations

Gnomad4 AFR exome

AF:

0.0986

Gnomad4 AMR exome

AF:

0.0921

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.000734

Gnomad4 SAS exome

AF:

0.0784

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.154

AC:

23516

AN:

152226

Hom.:

2025

Cov.:

AF XY:

0.152

AC XY:

11339

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0711

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.175

Hom.:

643

Bravo

AF:

0.149

Asia WGS

AF:

0.0390

AC:

138

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Oct 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epiphyseal dysplasia, multiple, 6

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over