Genetic Variant COL9A1:c.975+45G>A (chr6-70280767-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001851.6(COL9A1):c.975+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,585,528 control chromosomes in the GnomAD database, including 30,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3750 hom., cov: 31)

Exomes 𝑓: 0.19 ( 26598 hom. )

Consequence

COL9A1
NM_001851.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.108

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=-0.82).

BP6

Variant 6-70280767-C-T is Benign according to our data. Variant chr6-70280767-C-T is described in ClinVar as [Benign]. Clinvar id is 258363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6 link	c.975+45G>A		intron_variant	Intron 10 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.975+45G>A		intron_variant	Intron 10 of 37	1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32245

AN:

151724

Hom.:

3748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.166

AC:

34682

AN:

209318

Hom.:

3391

AF XY:

0.166

AC XY:

18888

AN XY:

113686

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.000703

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.187

AC:

267488

AN:

1433686

Hom.:

26598

Cov.:

AF XY:

0.185

AC XY:

131409

AN XY:

711596

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.000835

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.212

AC:

32259

AN:

151842

Hom.:

3750

Cov.:

AF XY:

0.210

AC XY:

15601

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.00175

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.197

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.203

Hom.:

622

Bravo

AF:

0.215

Asia WGS

AF:

0.0670

AC:

237

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 26, 2018

GeneDx

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

-0.82

CADD

Benign

6.7

DANN

Benign

0.57

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