Genetic Variant COL9A1:c.1612-26C>A (chr6-70255042-G-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.1612-26C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,340 control chromosomes in the GnomAD database, including 24,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1628 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22596 hom. )

Consequence

COL9A1
NM_001851.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.17

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=-0.74).

BP6

Variant 6-70255042-G-T is Benign according to our data. Variant chr6-70255042-G-T is described in ClinVar as [Benign]. Clinvar id is 258346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6 link	c.1612-26C>A		intron_variant	Intron 23 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.1612-26C>A		intron_variant	Intron 23 of 37	1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19241

AN:

151994

Hom.:

1626

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0319

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0539

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.133

AC:

33400

AN:

251352

Hom.:

2877

AF XY:

0.136

AC XY:

18442

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.0748

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0588

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.168

AC:

244811

AN:

1461228

Hom.:

22596

Cov.:

AF XY:

0.165

AC XY:

120048

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.0245

Gnomad4 AMR exome

AF:

0.0778

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0602

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.126

AC:

19239

AN:

152112

Hom.:

1628

Cov.:

AF XY:

0.125

AC XY:

9324

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0319

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0543

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.124

Hom.:

356

Bravo

AF:

0.117

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

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

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

-0.74

CADD

Benign

9.4

DANN

Benign

0.75

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