11-55638931-A-G

Variant names:

• chr11-55638931-A-G
• rs376540289
• NM_001405919.1:c.574A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001405919.1(OR4P4):​c.574A>G​(p.Met192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 1,486,458 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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. M192L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000045 (1 hom.)
• Consequence: OR4P4 NM_001405919.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0364089).

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.574A>G	p.Met192Val	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.574A>G	p.Met192Val	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.574A>G	p.Met192Val	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes AF: 0.00000719 AC: 1 AN: 139006 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000160

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000447 AC: 1 AN: 223688 AF XY: 0.00000825

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000445 AC: 6 AN: 1347452 Hom.: 1 Cov.: 30 AF XY: 0.00000298 AC XY: 2 AN XY: 670386

African (AFR) AF: 0.00 AC: 0 AN: 32782

American (AMR) AF: 0.00 AC: 0 AN: 36730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24038

East Asian (EAS) AF: 0.00 AC: 0 AN: 34542

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4992

European-Non Finnish (NFE) AF: 0.00000485 AC: 5 AN: 1031156

Other (OTH) AF: 0.00 AC: 0 AN: 55708

GnomAD4 genome AF: 0.00000719 AC: 1 AN: 139006 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 67444

African (AFR) AF: 0.00 AC: 0 AN: 40008

American (AMR) AF: 0.00 AC: 0 AN: 12852

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4260

South Asian (SAS) AF: 0.00 AC: 0 AN: 4246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000160 AC: 1 AN: 62396

Other (OTH) AF: 0.00 AC: 0 AN: 1872

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000886 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0080
DANN	Benign	0.25
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-2.4
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.057
MutPred		0.21		Gain of catalytic residue at M192 (P = 0.128)
MVP		0.15
MPC		0.019
ClinPred		0.039	T
GERP RS		-5.3
Varity_R		0.033
gMVP		0.11
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: rs376540289; hg19: chr11-55406407;