19-110922-C-T

Variant summary

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

The NM_001005240.3(OR4F17):​c.244C>T​(p.Arg82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 25)
Exomes 𝑓: 0.000081 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR4F17
NM_001005240.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.09
Variant links:
Genes affected
OR4F17 (HGNC:15381): (olfactory receptor family 4 subfamily F member 17) 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]

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=0.0889526).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4F17NM_001005240.3 linkuse as main transcriptc.244C>T p.Arg82Cys missense_variant 3/3 ENST00000585993.3 NP_001005240.1 Q8NGA8A0A126GWN0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4F17ENST00000585993.3 linkuse as main transcriptc.244C>T p.Arg82Cys missense_variant 3/36 NM_001005240.3 ENSP00000467301.1 Q8NGA8
OR4F17ENST00000618231.3 linkuse as main transcriptc.307C>T p.Arg103Cys missense_variant 2/26 ENSP00000493422.2 A0A2U3U062
OR4F17ENST00000318050.4 linkuse as main transcriptc.244C>T p.Arg82Cys missense_variant 1/16 ENSP00000315047.3 Q8NGA8
OR4F17ENST00000641591.1 linkuse as main transcriptn.194+241C>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
11
AN:
145018
Hom.:
0
Cov.:
25
FAILED QC
Gnomad AFR
AF:
0.0000995
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000709
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000101
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000762
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000807
AC:
97
AN:
1202062
Hom.:
0
Cov.:
20
AF XY:
0.0000790
AC XY:
48
AN XY:
607654
show subpopulations
Gnomad4 AFR exome
AF:
0.000101
Gnomad4 AMR exome
AF:
0.0000230
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000141
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000851
Gnomad4 OTH exome
AF:
0.0000781
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000758
AC:
11
AN:
145130
Hom.:
0
Cov.:
25
AF XY:
0.0000428
AC XY:
3
AN XY:
70158
show subpopulations
Gnomad4 AFR
AF:
0.0000992
Gnomad4 AMR
AF:
0.0000708
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000101
Gnomad4 NFE
AF:
0.0000762
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 submitterclinical testingAmbry GeneticsMar 07, 2024The c.244C>T (p.R82C) alteration is located in exon 1 (coding exon 1) of the OR4F17 gene. This alteration results from a C to T substitution at nucleotide position 244, causing the arginine (R) at amino acid position 82 to be replaced by a cysteine (C). 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
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
3.5
DANN
Benign
0.86
DEOGEN2
Benign
0.015
T;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0098
N
LIST_S2
Benign
0.30
.;T;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.089
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.6
L;.;L
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-4.0
.;.;D
REVEL
Benign
0.022
Sift
Benign
0.10
.;.;T
Sift4G
Benign
0.16
T;.;T
Polyphen
0.0
B;.;B
Vest4
0.055
MutPred
0.35
Gain of ubiquitination at K83 (P = 0.0514);.;Gain of ubiquitination at K83 (P = 0.0514);
MVP
0.15
MPC
2.3
ClinPred
0.039
T
GERP RS
0.19
Varity_R
0.12
gMVP
0.042

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.

Other links and lift over

dbSNP: rs1236062187; hg19: chr19-110922; API