rs760087

chr20-62836448-A-G

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.1549-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,612,998 control chromosomes in the GnomAD database, including 25,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2440 hom., cov: 34)
  • Exomes 𝑓: 0.17 (22765 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

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 20-62836448-A-G is Benign according to our data. Variant chr20-62836448-A-G is described in ClinVar as [Benign]. Clinvar id is 258413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.1549-30A>G		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.1549-30A>G		intron_variant			NM_001853.4	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24563 AN: 152114 Hom.: 2438 Cov.: 34

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.178

GnomAD3 exomes AF: 0.192 AC: 47337 AN: 247158 Hom.: 5593 AF XY: 0.186 AC XY: 24926 AN XY: 134190

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.459

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.166 AC: 242652 AN: 1460766 Hom.: 22765 Cov.: 36 AF XY: 0.165 AC XY: 119956 AN XY: 726664

Gnomad4 AFR exome AF: 0.0917

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.161 AC: 24566 AN: 152232 Hom.: 2440 Cov.: 34 AF XY: 0.164 AC XY: 12181 AN XY: 74438

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.180

Alfa AF: 0.166 Hom.: 2096

Bravo AF: 0.170

Asia WGS AF: 0.289 AC: 1005 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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.77
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs760087; hg19: chr20-61467800; COSMIC: COSV58983568; COSMIC: COSV58983568;