dbSNP rs1475792281: OR4F21:p.Val219Phe (chr8-166370-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005504.1(OR4F21):c.655G>T(p.Val219Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 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. V219I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 4)

Exomes 𝑓: 0.000018 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

OR4F21
NM_001005504.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

1 publications found

Variant links:

Genes affected

OR4F21 (HGNC:19583): (olfactory receptor family 4 subfamily F member 21) 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]

OR4F21 links:

ENSG00000292979 (HGNC:):

ENSG00000292979 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09799057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005504.1. 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
	OR4F21	NM_001005504.1	MANE Select	c.655G>T	p.Val219Phe	missense	Exon 1 of 1	NP_001005504.1	O95013

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR4F21	ENST00000320901.4	TSL:6 MANE Select	c.655G>T	p.Val219Phe	missense	Exon 1 of 1	ENSP00000318878.3	O95013
ENSG00000292979	ENST00000805562.1		n.115+65759G>T		intron	N/A
ENSG00000292979	ENST00000805563.1		n.136+66606G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000180

AC:

AN:

388588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

202848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10540

American (AMR)

AF:

0.00

AC:

AN:

16610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12544

East Asian (EAS)

AF:

0.000286

AC:

AN:

24472

South Asian (SAS)

AF:

0.00

AC:

AN:

37548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

236144

Other (OTH)

AF:

0.00

AC:

AN:

22822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.025

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.67

M_CAP

Benign

0.00078

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

-1.2

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.039

Sift

Uncertain

0.014

Sift4G

Uncertain

0.031

Polyphen

0.0030

Vest4

0.30

MutPred

0.52

Loss of catalytic residue at V219 (P = 0.2214)

MVP

0.067

ClinPred

0.81

GERP RS

-1.1

Varity_R

0.17

gMVP

0.20

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over