rs114458036

chr20-62828988-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001853.4(COL9A3):c.1008+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,593,186 control chromosomes in the GnomAD database, including 33,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4556 hom., cov: 34)
  • Exomes 𝑓: 0.20 (28978 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.67

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-62828988-G-C is Benign according to our data. Variant chr20-62828988-G-C is described in ClinVar as [Benign]. Clinvar id is 258403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62828988-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.1008+12G>C		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.1008+12G>C		intron_variant			NM_001853.4	P1
COL9A3	ENST00000463487.2			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35178 AN: 152098 Hom.: 4545 Cov.: 34

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.196 AC: 42116 AN: 214616 Hom.: 4234 AF XY: 0.194 AC XY: 22990 AN XY: 118212

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.197 AC: 284500 AN: 1440970 Hom.: 28978 Cov.: 38 AF XY: 0.197 AC XY: 140865 AN XY: 715886

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.231 AC: 35224 AN: 152216 Hom.: 4556 Cov.: 34 AF XY: 0.228 AC XY: 16976 AN XY: 74426

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.208

Alfa AF: 0.212 Hom.: 655

Bravo AF: 0.237

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2017	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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.30

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

Other links and lift over

dbSNP: rs114458036; hg19: chr20-61460340;