NM_001004059.3:c.294A>C

Variant names:

• chr11-55651197-A-C
• rs768267248
• NM_001004059.3:c.294A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001004059.3(OR4S2):​c.294A>C​(p.Gln98His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,486,718 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000022 (1 hom., cov: 25)
  • Exomes 𝑓: 0.000030 (6 hom.)
• Consequence: OR4S2 NM_001004059.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.633
• Publications: 1 publications found

Genes affected

OR4S2 (HGNC:15183): (olfactory receptor family 4 subfamily S 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4S2	NM_001004059.3	MANE Select	c.294A>C	p.Gln98His	missense	Exon 2 of 2	NP_001004059.2	A0A126GVG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4S2	ENST00000641692.1	MANE Select	c.294A>C	p.Gln98His	missense	Exon 2 of 2	ENSP00000493389.1	Q8NH73

Frequencies

GnomAD3 genomes AF: 0.0000217 AC: 3 AN: 138438 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000482

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000297 AC: 40 AN: 1348280 Hom.: 6 Cov.: 29 AF XY: 0.0000313 AC XY: 21 AN XY: 671062

African (AFR) AF: 0.00 AC: 0 AN: 32794

American (AMR) AF: 0.00 AC: 0 AN: 37454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24396

East Asian (EAS) AF: 0.00 AC: 0 AN: 34520

South Asian (SAS) AF: 0.00 AC: 0 AN: 80578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5018

European-Non Finnish (NFE) AF: 0.0000379 AC: 39 AN: 1029572

Other (OTH) AF: 0.0000179 AC: 1 AN: 55774

GnomAD4 genome AF: 0.0000217 AC: 3 AN: 138438 Hom.: 1 Cov.: 25 AF XY: 0.0000446 AC XY: 3 AN XY: 67252

African (AFR) AF: 0.00 AC: 0 AN: 39884

American (AMR) AF: 0.00 AC: 0 AN: 12742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3200

East Asian (EAS) AF: 0.00 AC: 0 AN: 4240

South Asian (SAS) AF: 0.00 AC: 0 AN: 4210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000482 AC: 3 AN: 62182

Other (OTH) AF: 0.00 AC: 0 AN: 1856

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	0.00067	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.066	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		-0.63
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.50		Gain of catalytic residue at L97 (P = 0.1768)
MVP		0.29
MPC		0.21
ClinPred		0.99	D
GERP RS		-0.85
Varity_R		0.60
gMVP		0.34
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs768267248; hg19: chr11-55418673;