rs746442650

Variant names:

• chr11-55638632-A-G
• rs746442650
• NM_001405919.1:c.275A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-55638632-A-G
• chr11-55638632-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001405919.1(OR4P4):​c.275A>G​(p.Tyr92Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,490,876 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000051 (1 hom., cov: 25)
  • Exomes 𝑓: 0.000013 (3 hom.)
• Consequence: OR4P4 NM_001405919.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0980
• Publications: 1 publications found

Genes affected

OR4P4 (HGNC:15180): (olfactory receptor family 4 subfamily P member 4) 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13935158).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405919.1. 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
	OR4P4	NM_001405919.1	MANE Select	c.275A>G	p.Tyr92Cys	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.275A>G	p.Tyr92Cys	missense	Exon 1 of 1	NP_001004124.1	Q8NGL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4P4	ENST00000641760.1	MANE Select	c.275A>G	p.Tyr92Cys	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes AF: 0.0000579 AC: 8 AN: 138288 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.000151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000786

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: 0.0000161

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000877 AC: 2 AN: 228004 AF XY: 0.0000162

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000133 AC: 18 AN: 1352506 Hom.: 3 Cov.: 30 AF XY: 0.0000163 AC XY: 11 AN XY: 672880

African (AFR) AF: 0.0000608 AC: 2 AN: 32884

American (AMR) AF: 0.00 AC: 0 AN: 37220

Ashkenazi Jewish (ASJ) AF: 0.000123 AC: 3 AN: 24386

East Asian (EAS) AF: 0.00 AC: 0 AN: 34552

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5042

European-Non Finnish (NFE) AF: 0.0000106 AC: 11 AN: 1033848

Other (OTH) AF: 0.0000179 AC: 1 AN: 55904

GnomAD4 genome AF: 0.0000506 AC: 7 AN: 138370 Hom.: 1 Cov.: 25 AF XY: 0.0000744 AC XY: 5 AN XY: 67198

African (AFR) AF: 0.000125 AC: 5 AN: 39888

American (AMR) AF: 0.0000786 AC: 1 AN: 12730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3208

East Asian (EAS) AF: 0.00 AC: 0 AN: 4220

South Asian (SAS) AF: 0.00 AC: 0 AN: 4218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.0000161 AC: 1 AN: 62194

Other (OTH) AF: 0.00 AC: 0 AN: 1838

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000876 AC: 1

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	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.78
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.098
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.13	B
Vest4		0.31
MutPred		0.53		Loss of catalytic residue at Y92 (P = 0.0428)
MVP		0.28
MPC		0.022
ClinPred		0.33	T
GERP RS		2.7
Varity_R		0.58
gMVP		0.059
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs746442650; hg19: chr11-55406108;