Genetic Variant OR4F17:p.Ser86Cys (chr19-110935-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001005240.3(OR4F17):c.257C>G(p.Ser86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00020 ( 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: 1.92

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2890955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4F17	NM_001005240.3 link	c.257C>G	p.Ser86Cys	missense_variant	Exon 3 of 3	ENST00000585993.3	NP_001005240.1	Q8NGA8A0A126GWN0
OR4F17	NM_001429985.1 link	c.320C>G	p.Ser107Cys	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.257C>G	p.Ser86Cys	missense_variant	Exon 3 of 3	6	NM_001005240.3	ENSP00000467301.1	Q8NGA8
OR4F17	ENST00000618231.3 link	c.320C>G	p.Ser107Cys	missense_variant	Exon 2 of 2	6		ENSP00000493422.2	A0A2U3U062
OR4F17	ENST00000318050.4 link	c.257C>G	p.Ser86Cys	missense_variant	Exon 1 of 1	6		ENSP00000315047.3	Q8NGA8
OR4F17	ENST00000641591.1 link	n.194+254C>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145584

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000141

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000731

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.000516

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000197

AC:

220

AN:

1115564

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

153

AN XY:

567138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000470

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00207

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000211

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000480

AC:

AN:

145698

Hom.:

Cov.:

AF XY:

0.0000852

AC XY:

AN XY:

70448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000141

Gnomad4 ASJ

AF:

0.000294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000732

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.257C>G (p.S86C) alteration is located in exon 1 (coding exon 1) of the OR4F17 gene. This alteration results from a C to G substitution at nucleotide position 257, causing the serine (S) at amino acid position 86 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.026

T;.;T

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.073

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.80

.;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.0

H;.;H

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.8

.;.;D

REVEL

Benign

0.090

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.58

MutPred

0.65

Loss of stability (P = 0.1038);.;Loss of stability (P = 0.1038);

MVP

0.68

MPC

3.3

ClinPred

0.70

GERP RS

2.4

Varity_R

0.57

gMVP

0.060

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