rs2294988

chr20-62822197-G-Achr20-62822197-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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12

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=-0.84).
• 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	UniProt
COL9A3	NM_001853.4	c.477+33G>A		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.477+33G>A		intron_variant			NM_001853.4	P1
COL9A3	ENST00000452372.2	c.366+33G>A		intron_variant		5
COL9A3	ENST00000477612.5	n.473+33G>A		intron_variant, non_coding_transcript_variant		3
COL9A3	ENST00000489045.5	n.523+33G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41888 AN: 151962 Hom.: 6186 Cov.: 32

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

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.: 19 AF XY: 0.317 AC XY: 190175 AN XY: 600194

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.: 32 AF XY: 0.276 AC XY: 20539 AN XY: 74348

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: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	-0.84
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

Other links and lift over

dbSNP: rs2294988; hg19: chr20-61453549; COSMIC: COSV59651566; COSMIC: COSV59651566;