chr11-55651326-A-C

Variant names:

• chr11-55651326-A-C
• rs752338177
• NM_001004059.3:c.423A>C

Variant summary

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

The NM_001004059.3(OR4S2):​c.423A>C​(p.Lys141Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,488,176 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000036 (10 hom.)
• Consequence: OR4S2 NM_001004059.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.14
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0259687).
• BS2: High Homozygotes in GnomAdExome4 at 10 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.423A>C	p.Lys141Asn	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.423A>C	p.Lys141Asn	missense	Exon 2 of 2	ENSP00000493389.1	Q8NH73

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 2 AN: 138014 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000158

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000197 AC: 45 AN: 228652 AF XY: 0.000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000357

GnomAD4 exome AF: 0.0000363 AC: 49 AN: 1350162 Hom.: 10 Cov.: 30 AF XY: 0.0000313 AC XY: 21 AN XY: 671974

African (AFR) AF: 0.00 AC: 0 AN: 32822

American (AMR) AF: 0.00131 AC: 49 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24400

East Asian (EAS) AF: 0.00 AC: 0 AN: 34548

South Asian (SAS) AF: 0.00 AC: 0 AN: 80618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5026

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1031312

Other (OTH) AF: 0.00 AC: 0 AN: 55810

GnomAD4 genome AF: 0.0000145 AC: 2 AN: 138014 Hom.: 0 Cov.: 25 AF XY: 0.0000299 AC XY: 2 AN XY: 66872

African (AFR) AF: 0.00 AC: 0 AN: 39768

American (AMR) AF: 0.000158 AC: 2 AN: 12658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3202

East Asian (EAS) AF: 0.00 AC: 0 AN: 4180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62098

Other (OTH) AF: 0.00 AC: 0 AN: 1832

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000156 AC: 18

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	Benign	0.20
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.079	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.12
Sift	Benign	0.039	D
Sift4G	Benign	0.062	T
Polyphen		0.97	D
Vest4		0.072
MutPred		0.28		Loss of ubiquitination at K141 (P = 0.0412)
MVP		0.15
MPC		0.044
ClinPred		0.083	T
GERP RS		-8.3
Varity_R		0.11
gMVP		0.23
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs752338177; hg19: chr11-55418802;