11-55651169-C-A

Variant names:

• chr11-55651169-C-A
• rs150655948
• NM_001004059.3:c.266C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004059.3(OR4S2):​c.266C>A​(p.Thr89Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000876 in 1,484,636 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T89S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000089 (2 hom.)
• Consequence: OR4S2 NM_001004059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 4 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.063120514).
• BS2: High Homozygotes in GnomAdExome4 at 2 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.266C>A	p.Thr89Asn	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.266C>A	p.Thr89Asn	missense	Exon 2 of 2	ENSP00000493389.1	Q8NH73

Frequencies

GnomAD3 genomes AF: 0.00000723 AC: 1 AN: 138368 Hom.: 0 Cov.: 26

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: 0.000111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000437 AC: 1 AN: 228886 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000514

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 12 AN: 1346268 Hom.: 2 Cov.: 29 AF XY: 0.00000895 AC XY: 6 AN XY: 670298

African (AFR) AF: 0.00 AC: 0 AN: 32756

American (AMR) AF: 0.00 AC: 0 AN: 37440

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 34522

South Asian (SAS) AF: 0.00 AC: 0 AN: 80510

European-Finnish (FIN) AF: 0.0000623 AC: 3 AN: 48174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5022

European-Non Finnish (NFE) AF: 0.00000876 AC: 9 AN: 1027742

Other (OTH) AF: 0.00 AC: 0 AN: 55706

GnomAD4 genome AF: 0.00000723 AC: 1 AN: 138368 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 67180

African (AFR) AF: 0.00 AC: 0 AN: 39856

American (AMR) AF: 0.00 AC: 0 AN: 12768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3204

East Asian (EAS) AF: 0.00 AC: 0 AN: 4232

South Asian (SAS) AF: 0.00 AC: 0 AN: 4198

European-Finnish (FIN) AF: 0.000111 AC: 1 AN: 8982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62166

Other (OTH) AF: 0.00 AC: 0 AN: 1860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-1.3
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.037
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.032	D
Polyphen		0.0040	B
Vest4		0.21
MutPred		0.52		Loss of ubiquitination at K86 (P = 0.0907)
MVP		0.25
MPC		0.063
ClinPred		0.16	T
GERP RS		2.3
Varity_R		0.49
gMVP		0.068
Mutation Taster		=100/0	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: rs150655948; hg19: chr11-55418645;