rs115466848

chr20-62826839-G-Achr20-62826839-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001853.4(COL9A3):c.792+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,612,204 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.356

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 20-62826839-G-A is Benign according to our data. Variant chr20-62826839-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1697/152246) while in subpopulation AFR AF= 0.0377 (1566/41530). AF 95% confidence interval is 0.0362. There are 43 homozygotes in gnomad4. There are 805 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.792+19G>A		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.792+19G>A		intron_variant			NM_001853.4	P1
COL9A3	ENST00000463487.2	n.500+19G>A		intron_variant, non_coding_transcript_variant		5
COL9A3	ENST00000489045.5			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1689 AN: 152128 Hom.: 43 Cov.: 33

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00293 AC: 724 AN: 247252 Hom.: 18 AF XY: 0.00222 AC XY: 299 AN XY: 134450

Gnomad AFR exome AF: 0.0380

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00115

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000718

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00106 AC: 1553 AN: 1459958 Hom.: 23 Cov.: 32 AF XY: 0.000889 AC XY: 646 AN XY: 726296

Gnomad4 AFR exome AF: 0.0351

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000680

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.0111 AC: 1697 AN: 152246 Hom.: 43 Cov.: 33 AF XY: 0.0108 AC XY: 805 AN XY: 74448

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00468 Hom.: 1

Bravo AF: 0.0131

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

-

- -

Intervertebral disc disorder;C1832998:Epiphyseal dysplasia, multiple, 3 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 11, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.0
Dann	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs115466848; hg19: chr20-61458191;