9-122510859-C-T

Variant names:

• chr9-122510859-C-T
• rs200778732
• NM_054107.1:c.58C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_054107.1(OR1J2):​c.58C>T​(p.Arg20Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,609,682 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: OR1J2 NM_054107.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.17

Genes affected

OR1J2 (HGNC:8209): (olfactory receptor family 1 subfamily J member 2) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ENSG00000234156 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003982991).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1J2	NM_054107.1	c.58C>T	p.Arg20Trp	missense_variant	Exon 1 of 1	ENST00000335302.5	NP_473448.1
OR1J2	XM_024447516.2	c.58C>T	p.Arg20Trp	missense_variant	Exon 3 of 3		XP_024303284.1
OR1J2	XM_024447517.2	c.58C>T	p.Arg20Trp	missense_variant	Exon 4 of 4		XP_024303285.1
OR1J2	XR_007061271.1	n.1540+7989C>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1J2	ENST00000335302.5	c.58C>T	p.Arg20Trp	missense_variant	Exon 1 of 1	6	NM_054107.1	ENSP00000335575.5
ENSG00000234156	ENST00000431442.2	n.1362+7989C>T		intron_variant	Intron 7 of 9	3

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000308 AC: 77 AN: 250086 Hom.: 0 AF XY: 0.000266 AC XY: 36 AN XY: 135090

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00573

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000974

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000139 AC: 202 AN: 1457388 Hom.: 2 Cov.: 31 AF XY: 0.000132 AC XY: 96 AN XY: 725120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000897

Gnomad4 ASJ exome AF: 0.00496

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000334

Gnomad4 OTH exome AF: 0.000349

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74464

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000461 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58C>T (p.R20W) alteration is located in exon 1 (coding exon 1) of the OR1J2 gene. This alteration results from a C to T substitution at nucleotide position 58, causing the arginine (R) at amino acid position 20 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.074	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.12	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.013
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.16
MVP		0.11
MPC		0.018
ClinPred		0.045	T
GERP RS		-6.5
Varity_R		0.053
gMVP		0.15

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: rs200778732; hg19: chr9-125273138; COSMIC: COSV58943743;