rs1018440

chr20-62833088-G-A

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.1368+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,599,502 control chromosomes in the GnomAD database, including 38,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (7162 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31628 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.295

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=-0.89).
• BP6: Variant 20-62833088-G-A is Benign according to our data. Variant chr20-62833088-G-A is described in ClinVar as [Benign]. Clinvar id is 258406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.1368+24G>A		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.1368+24G>A		intron_variant			NM_001853.4	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41127 AN: 152100 Hom.: 7144 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.184 AC: 46055 AN: 250726 Hom.: 5545 AF XY: 0.179 AC XY: 24298 AN XY: 135796

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0565

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.198 AC: 286257 AN: 1447284 Hom.: 31628 Cov.: 27 AF XY: 0.195 AC XY: 140248 AN XY: 720858

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.0487

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.271 AC: 41189 AN: 152218 Hom.: 7162 Cov.: 33 AF XY: 0.263 AC XY: 19565 AN XY: 74436

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.245

Alfa AF: 0.243 Hom.: 1180

Bravo AF: 0.279

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.0
Dann	Benign	0.68

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: rs1018440; hg19: chr20-61464440; COSMIC: COSV59653078; COSMIC: COSV59653078;