Genetic Variant OR4F21:p.Gly231Arg (chr8-166334-C-G) – 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.691G>C(p.Gly231Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 4)

Exomes 𝑓: 0.000028 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR4F21
NM_001005504.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.213

Publications

0 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=0.08693203).

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.691G>C	p.Gly231Arg	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.691G>C	p.Gly231Arg	missense	Exon 1 of 1	ENSP00000318878.3	O95013
ENSG00000292979	ENST00000805562.1		n.115+65795G>C		intron	N/A
ENSG00000292979	ENST00000805563.1		n.136+66642G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

15526

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000281

AC:

AN:

391504

Hom.:

Cov.:

AF XY:

0.0000391

AC XY:

AN XY:

204402

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

11802

American (AMR)

AF:

0.0000592

AC:

AN:

16898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12766

East Asian (EAS)

AF:

0.00

AC:

AN:

24262

South Asian (SAS)

AF:

0.0000535

AC:

AN:

37406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

237200

Other (OTH)

AF:

0.000261

AC:

AN:

22970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.581

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

15566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7154

African (AFR)

AF:

0.00

AC:

AN:

7914

American (AMR)

AF:

0.00

AC:

AN:

820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

298

East Asian (EAS)

AF:

0.00

AC:

AN:

170

South Asian (SAS)

AF:

0.00

AC:

AN:

178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

4960

Other (OTH)

AF:

0.00

AC:

AN:

178

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.030

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.41

M_CAP

Benign

0.00084

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.61

PhyloP100

-0.21

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.034

Sift

Uncertain

0.020

Sift4G

Benign

0.16

Polyphen

0.031

Vest4

0.11

MutPred

0.45

Gain of MoRF binding (P = 0.0087)

MVP

0.35

ClinPred

0.26

GERP RS

1.0

Varity_R

0.43

gMVP

0.086

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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