Variant chr8-166551-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005504.1(OR4F21):c.474C>G(p.Phe158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 6)

Exomes 𝑓: 0.00070 ( 79 hom. )

Failed GnomAD Quality Control

Consequence

OR4F21
NM_001005504.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06525797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F21	NM_001005504.1 linkuse as main transcript	c.474C>G	p.Phe158Leu	missense_variant	1/1	ENST00000320901.4	NP_001005504.1	O95013

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4F21	ENST00000320901.4 linkuse as main transcript	c.474C>G	p.Phe158Leu	missense_variant	1/1	6	NM_001005504.1	ENSP00000318878.3		O95013

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

42816

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00104

Gnomad ASJ

AF:

0.00140

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0167

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000704

AC:

490

AN:

696042

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

299

AN XY:

366374

show subpopulations

Gnomad4 AFR exome

AF:

0.000779

Gnomad4 AMR exome

AF:

0.000661

Gnomad4 ASJ exome

AF:

0.00160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000486

Gnomad4 OTH exome

AF:

0.000991

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000257

AC:

AN:

42860

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

AN XY:

20080

show subpopulations

Gnomad4 AFR

AF:

0.0000747

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.00140

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00219

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.474C>G (p.F158L) alteration is located in exon 1 (coding exon 1) of the OR4F21 gene. This alteration results from a C to G substitution at nucleotide position 474, causing the phenylalanine (F) at amino acid position 158 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.62

M_CAP

Benign

0.00081

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.66

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.050

REVEL

Benign

0.049

Sift

Benign

0.21

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.098

MutPred

0.33

Loss of catalytic residue at F158 (P = 0.0093);

MVP

0.072

ClinPred

0.15

GERP RS

2.0

Varity_R

0.077

gMVP

0.052

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over