Variant 15-101922581-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000650172.1(OR4F4):c.533C>T(p.Pro178Leu) 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 0.0011 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR4F4
ENST00000650172.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

OR4F4 (HGNC:8301): (olfactory receptor family 4 subfamily F member 4) 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]

OR4F4 links:

OR4F4 (HGNC:):

OR4F4 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=0.32036003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F4	use as main transcript	n.101922581G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4F4	ENST00000650172.1 linkuse as main transcript	c.533C>T	p.Pro178Leu	missense_variant	1/1			ENSP00000497674.1		A0A3B3ITA0

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

115

AN:

103260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000302

Gnomad AMI

AF:

0.00124

Gnomad AMR

AF:

0.00331

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00158

Gnomad SAS

AF:

0.00346

Gnomad FIN

AF:

0.000143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000989

Gnomad OTH

AF:

0.00281

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000419

AC:

446

AN:

1063782

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

242

AN XY:

537726

show subpopulations

Gnomad4 AFR exome

AF:

0.000204

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.0000440

Gnomad4 EAS exome

AF:

0.000215

Gnomad4 SAS exome

AF:

0.00142

Gnomad4 FIN exome

AF:

0.000396

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000538

GnomAD4 genome

AF:

0.00111

AC:

115

AN:

103328

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

48616

show subpopulations

Gnomad4 AFR

AF:

0.000301

Gnomad4 AMR

AF:

0.00330

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00158

Gnomad4 SAS

AF:

0.00347

Gnomad4 FIN

AF:

0.000143

Gnomad4 NFE

AF:

0.000989

Gnomad4 OTH

AF:

0.00277

Alfa

AF:

0.00178

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

Apr 12, 2022

The c.479C>T (p.P160L) alteration is located in exon 1 (coding exon 1) of the OR4F4 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the proline (P) at amino acid position 160 to be replaced by a leucine (L). 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

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.00086

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

M;.

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-9.4

D;.

REVEL

Benign

0.11

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.0040

D;.

Polyphen

0.0010

B;.

Vest4

0.43

MutPred

0.52

Gain of catalytic residue at P160 (P = 0.0632);.;

MVP

0.32

ClinPred

1.0

GERP RS

2.8

Varity_R

0.46

gMVP

0.051

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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