Variant 19-110923-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005240.3(OR4F17):c.245G>A(p.Arg82His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000072 ( 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: -3.43

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:

OR4F17 (HGNC:):

OR4F17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021383882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F17	NM_001005240.3 linkuse as main transcript	c.245G>A	p.Arg82His	missense_variant	3/3	ENST00000585993.3	NP_001005240.1	Q8NGA8A0A126GWN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR4F17	ENST00000585993.3 linkuse as main transcript	c.245G>A	p.Arg82His	missense_variant	3/3	6	NM_001005240.3	ENSP00000467301.1	Q8NGA8
OR4F17	ENST00000618231.3 linkuse as main transcript	c.308G>A	p.Arg103His	missense_variant	2/2	6		ENSP00000493422.2	A0A2U3U062
OR4F17	ENST00000318050.4 linkuse as main transcript	c.245G>A	p.Arg82His	missense_variant	1/1	6		ENSP00000315047.3	Q8NGA8
OR4F17	ENST00000641591.1 linkuse as main transcript	n.194+242G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144930

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000284

Gnomad ASJ

AF:

0.000295

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000245

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000304

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000718

AC:

AN:

1198040

Hom.:

Cov.:

AF XY:

0.0000759

AC XY:

AN XY:

605780

show subpopulations

Gnomad4 AFR exome

AF:

0.00160

Gnomad4 AMR exome

AF:

0.0000692

Gnomad4 ASJ exome

AF:

0.0000815

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000262

Gnomad4 OTH exome

AF:

0.0000587

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000455

AC:

AN:

145040

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

70098

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.000283

Gnomad4 ASJ

AF:

0.000295

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000246

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000305

Gnomad4 OTH

AF:

0.00

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

Feb 28, 2023

The c.245G>A (p.R82H) alteration is located in exon 1 (coding exon 1) of the OR4F17 gene. This alteration results from a G to A substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a histidine (H). 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

0.073

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.12

DANN

Benign

0.77

DEOGEN2

Benign

0.0037

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.32

.;T;T

M_CAP

Benign

0.00080

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.13

N;.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

1.6

.;.;N

REVEL

Benign

0.023

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;B

Vest4

0.036

MutPred

0.32

Loss of MoRF binding (P = 0.08);.;Loss of MoRF binding (P = 0.08);

MVP

0.19

MPC

2.2

ClinPred

0.0033

GERP RS

0.90

Varity_R

0.020

gMVP

0.035

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