Variant rs2294988 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001853.4(COL9A3):c.477+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,332,424 control chromosomes in the GnomAD database, including 67,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6186 hom., cov: 32)

Exomes 𝑓: 0.32 ( 60969 hom. )

Consequence

COL9A3
NM_001853.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.12

Variant links:

Genes affected

COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]

COL9A3 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=-0.84).

BP6

Variant 20-62822197-G-A is Benign according to our data. Variant chr20-62822197-G-A is described in ClinVar as [Benign]. Clinvar id is 258425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4 linkuse as main transcript	c.477+33G>A		intron_variant		ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
COL9A3	ENST00000649368.1 linkuse as main transcript	c.477+33G>A	intron_variant		NM_001853.4	ENSP00000496793	P1
COL9A3	ENST00000452372.2 linkuse as main transcript	c.366+33G>A	intron_variant	5		ENSP00000394280
COL9A3	ENST00000477612.5 linkuse as main transcript	n.473+33G>A	intron_variant, non_coding_transcript_variant	3
COL9A3	ENST00000489045.5 linkuse as main transcript	n.523+33G>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41888

AN:

151962

Hom.:

6186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.300

AC:

74420

AN:

248048

Hom.:

11605

AF XY:

0.299

AC XY:

40257

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.319

AC:

376466

AN:

1180346

Hom.:

60969

Cov.:

AF XY:

0.317

AC XY:

190175

AN XY:

600194

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.258

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.276

AC:

41905

AN:

152078

Hom.:

6186

Cov.:

AF XY:

0.276

AC XY:

20539

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.248

Hom.:

1042

Bravo

AF:

0.268

Asia WGS

AF:

0.251

AC:

875

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.10

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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