ENST00000641760.1:c.272C>T

Variant names:

• chr11-55638629-C-T
• rs774695651
• NM_001405919.1:c.272C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000641760.1(OR4P4):​c.272C>T​(p.Ser91Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,490,196 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000081 (2 hom.)
• Consequence: OR4P4 ENST00000641760.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 2 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2784781).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641760.1. 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.272C>T	p.Ser91Phe	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.272C>T	p.Ser91Phe	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.272C>T	p.Ser91Phe	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes AF: 0.00000723 AC: 1 AN: 138222 Hom.: 0 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: 0.0000161

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000176 AC: 4 AN: 227556 AF XY: 0.00000811

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: 0.0000381

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000814 AC: 11 AN: 1351974 Hom.: 2 Cov.: 30 AF XY: 0.00000595 AC XY: 4 AN XY: 672576

African (AFR) AF: 0.00 AC: 0 AN: 32880

American (AMR) AF: 0.00 AC: 0 AN: 37156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24358

East Asian (EAS) AF: 0.00 AC: 0 AN: 34544

South Asian (SAS) AF: 0.00 AC: 0 AN: 80498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5032

European-Non Finnish (NFE) AF: 0.00000871 AC: 9 AN: 1033526

Other (OTH) AF: 0.0000358 AC: 2 AN: 55894

GnomAD4 genome AF: 0.00000723 AC: 1 AN: 138222 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 67044

African (AFR) AF: 0.00 AC: 0 AN: 39746

American (AMR) AF: 0.00 AC: 0 AN: 12734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3198

East Asian (EAS) AF: 0.00 AC: 0 AN: 4228

South Asian (SAS) AF: 0.00 AC: 0 AN: 4236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8960

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

European-Non Finnish (NFE) AF: 0.0000161 AC: 1 AN: 62178

Other (OTH) AF: 0.00 AC: 0 AN: 1842

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.34
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.3
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		0.11	B
Vest4		0.50
MVP		0.31
MPC		0.16
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.53
gMVP		0.13
Mutation Taster		=91/9	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: rs774695651; hg19: chr11-55406105; COSMIC: COSV58921030;