19-110922-C-T

Variant names:

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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82H) has been classified 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

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]

OR4F17 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=0.0889526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4F17	NM_001005240.3 link	c.244C>T	p.Arg82Cys	missense_variant	Exon 3 of 3	ENST00000585993.3	NP_001005240.1	Q8NGA8A0A126GWN0
OR4F17	NM_001429985.1 link	c.307C>T	p.Arg103Cys	missense_variant	Exon 2 of 2		NP_001416914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR4F17	ENST00000585993.3 link	c.244C>T	p.Arg82Cys	missense_variant	Exon 3 of 3	6	NM_001005240.3	ENSP00000467301.1	Q8NGA8
OR4F17	ENST00000618231.3 link	c.307C>T	p.Arg103Cys	missense_variant	Exon 2 of 2	6		ENSP00000493422.2	A0A2U3U062
OR4F17	ENST00000318050.4 link	c.244C>T	p.Arg82Cys	missense_variant	Exon 1 of 1	6		ENSP00000315047.3	Q8NGA8
OR4F17	ENST00000641591.1 link	n.194+241C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145018

Hom.:

Cov.:

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:

AN:

1202062

Hom.:

Cov.:

AF XY:

0.0000790

AC XY:

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:

AN:

145130

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

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

Mar 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 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

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

LIST_S2

Benign

0.30

.;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.089

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

L;.;L

PrimateAI

Benign

0.41

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

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.

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