Variant 8-166478-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005504.1(OR4F21):c.547C>T(p.Arg183Trp) 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 0.000094 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000052 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

OR4F21
NM_001005504.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.423

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17184052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F21	NM_001005504.1 linkuse as main transcript	c.547C>T	p.Arg183Trp	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.547C>T	p.Arg183Trp	missense_variant	1/1	6	NM_001005504.1	ENSP00000318878.3		O95013

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

42582

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000778

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

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:

0.0000506

Gnomad OTH

AF:

0.00236

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000517

AC:

AN:

483390

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

256688

show subpopulations

Gnomad4 AFR exome

AF:

0.000143

Gnomad4 AMR exome

AF:

0.0000743

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000216

Gnomad4 FIN exome

AF:

0.0000634

Gnomad4 NFE exome

AF:

0.0000479

Gnomad4 OTH exome

AF:

0.000148

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000939

AC:

AN:

42582

Hom.:

Cov.:

AF XY:

0.0000506

AC XY:

AN XY:

19758

show subpopulations

Gnomad4 AFR

AF:

0.0000778

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000506

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000169

Hom.:

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 26, 2023

The c.547C>T (p.R183W) alteration is located in exon 1 (coding exon 1) of the OR4F21 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a tryptophan (W). 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

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.031

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.85

M_CAP

Benign

0.00072

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.081

Sift

Benign

0.076

Sift4G

Uncertain

0.034

Polyphen

0.28

Vest4

0.32

MutPred

0.47

Gain of catalytic residue at L181 (P = 0.0308);

MVP

0.35

ClinPred

0.95

GERP RS

0.98

Varity_R

0.16

gMVP

0.24

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

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