6-70241400-A-G

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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.908

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:

ENSG00000253809 (HGNC:):

ENSG00000253809 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=-0.79).

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 rank	MANE	Protein	UniProt
COL9A1	NM_001851.6 link	c.2034+19T>C		intron_variant	Intron 31 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.2034+19T>C		intron_variant	Intron 31 of 37	1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22405

AN:

152136

Hom.:

2016

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.181

AC XY:

130686

AN XY:

720234

show subpopulations

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.:

AF XY:

0.145

AC XY:

10801

AN XY:

74438

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 18, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

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

-0.79

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

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