Genetic Variant OR4F17:p.Leu180Phe (chr19-111216-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001005240.3(OR4F17):c.538C>T(p.Leu180Phe) 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 0.00032 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000096 ( 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: 0.855

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=0.18962348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4F17	NM_001005240.3 link	c.538C>T	p.Leu180Phe	missense_variant	Exon 3 of 3	ENST00000585993.3	NP_001005240.1	Q8NGA8A0A126GWN0
OR4F17	NM_001429985.1 link	c.601C>T	p.Leu201Phe	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.538C>T	p.Leu180Phe	missense_variant	Exon 3 of 3	6	NM_001005240.3	ENSP00000467301.1	Q8NGA8
OR4F17	ENST00000618231.3 link	c.601C>T	p.Leu201Phe	missense_variant	Exon 2 of 2	6		ENSP00000493422.2	A0A2U3U062
OR4F17	ENST00000318050.4 link	c.538C>T	p.Leu180Phe	missense_variant	Exon 1 of 1	6		ENSP00000315047.3	Q8NGA8
OR4F17	ENST00000641591.1 link	n.194+535C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146590

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000206

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:

0.00

Gnomad OTH

AF:

0.000499

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000957

AC:

AN:

511796

Hom.:

Cov.:

AF XY:

0.0000699

AC XY:

AN XY:

271872

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.000154

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000648

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000320

AC:

AN:

146676

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

71026

show subpopulations

Gnomad4 AFR

AF:

0.00105

Gnomad4 AMR

AF:

0.000206

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000495

Alfa

AF:

0.000337

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.538C>T (p.L180F) 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 538, causing the leucine (L) at amino acid position 180 to be replaced by a phenylalanine (F). 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

0.55

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;.;T

Eigen

Uncertain

0.43

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.77

.;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

4.4

H;.;H

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.0

.;.;D

REVEL

Benign

0.077

Sift

Uncertain

0.0060

.;.;D

Sift4G

Uncertain

0.0040

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.43

MutPred

0.45

Gain of methylation at K179 (P = 0.0321);.;Gain of methylation at K179 (P = 0.0321);

MVP

0.60

MPC

3.5

ClinPred

0.32

GERP RS

2.5

Varity_R

0.27

gMVP

0.024

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