rs117347229

chr20-62821485-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.346-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,612,528 control chromosomes in the GnomAD database, including 8,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (678 hom., cov: 33)
  • Exomes 𝑓: 0.10 (7940 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09

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=-0.54).
• BP6: Variant 20-62821485-G-A is Benign according to our data. Variant chr20-62821485-G-A is described in ClinVar as [Benign]. Clinvar id is 258423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.346-22G>A		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.346-22G>A		intron_variant			NM_001853.4	P1
COL9A3	ENST00000452372.2	c.235-22G>A		intron_variant		5
COL9A3	ENST00000477612.5	n.342-22G>A		intron_variant, non_coding_transcript_variant		3
COL9A3	ENST00000489045.5	n.392-22G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13125 AN: 152088 Hom.: 680 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0974

GnomAD3 exomes AF: 0.0910 AC: 22757 AN: 249952 Hom.: 1228 AF XY: 0.0968 AC XY: 13131 AN XY: 135600

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.0589

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.00479

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.0939

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.100 AC: 146200 AN: 1460322 Hom.: 7940 Cov.: 33 AF XY: 0.102 AC XY: 73987 AN XY: 726468

Gnomad4 AFR exome AF: 0.0455

Gnomad4 AMR exome AF: 0.0614

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.00307

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0956

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0962

GnomAD4 genome AF: 0.0862 AC: 13113 AN: 152206 Hom.: 678 Cov.: 33 AF XY: 0.0864 AC XY: 6430 AN XY: 74430

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.0790

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0959

Alfa AF: 0.0966 Hom.: 140

Bravo AF: 0.0804

Asia WGS AF: 0.0600 AC: 210 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 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	15
Dann	Benign	0.81

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

Other links and lift over

dbSNP: rs117347229; hg19: chr20-61452837; COSMIC: COSV59652879; COSMIC: COSV59652879;