rs397840562

chr20-62830443-T-TGchr20-62830443-T-TGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001853.4(COL9A3):c.1215+36dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,573,964 control chromosomes in the GnomAD database, including 27,501 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3376 hom., cov: 28)
  • Exomes 𝑓: 0.18 (24125 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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 -16 ACMG points.

• BP6: Variant 20-62830443-T-TG is Benign according to our data. Variant chr20-62830443-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 258404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.1215+36dup		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.1215+36dup		intron_variant			NM_001853.4	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30742 AN: 151546 Hom.: 3367 Cov.: 28

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.174 AC: 32273 AN: 185700 Hom.: 3060 AF XY: 0.172 AC XY: 17146 AN XY: 99708

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.103

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.182 AC: 258266 AN: 1422300 Hom.: 24125 Cov.: 35 AF XY: 0.181 AC XY: 127379 AN XY: 704012

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.0994

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.203 AC: 30783 AN: 151664 Hom.: 3376 Cov.: 28 AF XY: 0.201 AC XY: 14918 AN XY: 74120

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.185

Alfa AF: 0.193 Hom.: 501

Bravo AF: 0.204

Asia WGS AF: 0.170 AC: 593 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely 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

Oct 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs397840562; hg19: chr20-61461795;