dbSNP rs3765462: COL9A3:c.1548+16G>A (chr20-62836349-G-A) – 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_001853.4(COL9A3):c.1548+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,613,744 control chromosomes in the GnomAD database, including 960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 159 hom., cov: 34)

Exomes 𝑓: 0.021 ( 801 hom. )

Consequence

COL9A3
NM_001853.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.53

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=-0.8).

BP6

Variant 20-62836349-G-A is Benign according to our data. Variant chr20-62836349-G-A is described in ClinVar as [Benign]. Clinvar id is 258412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62836349-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.1548+16G>A		intron_variant	Intron 28 of 31	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.1548+16G>A		intron_variant	Intron 28 of 31		NM_001853.4	ENSP00000496793.1		Q14050

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5291

AN:

152248

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0314

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.0134

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0293

AC:

7299

AN:

249424

Hom.:

267

AF XY:

0.0264

AC XY:

3572

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.0695

Gnomad AMR exome

AF:

0.0379

Gnomad ASJ exome

AF:

0.0204

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.00716

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0206

AC:

30175

AN:

1461378

Hom.:

801

Cov.:

AF XY:

0.0202

AC XY:

14672

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0689

Gnomad4 AMR exome

AF:

0.0358

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.00834

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0272

GnomAD4 genome

AF:

0.0348

AC:

5307

AN:

152366

Hom.:

159

Cov.:

AF XY:

0.0345

AC XY:

2573

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0680

Gnomad4 AMR

AF:

0.0316

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.0134

Gnomad4 NFE

AF:

0.0149

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0234

Hom.:

Bravo

AF:

0.0379

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 04, 2018

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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