chr15-101922194-G-A

Variant summary

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

The ENST00000650172.1(OR4F4):​c.920C>T​(p.Thr307Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 146,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 24)
Exomes 𝑓: 0.00012 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR4F4
ENST00000650172.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.15
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]

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=0.03932917).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR4F4ENST00000650172.1 linkuse as main transcriptc.920C>T p.Thr307Met missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000478
AC:
7
AN:
146326
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.0000552
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000737
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000148
AC:
37
AN:
250454
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135430
show subpopulations
Gnomad AFR exome
AF:
0.0000638
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000282
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000123
AC:
179
AN:
1457960
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
88
AN XY:
725344
show subpopulations
Gnomad4 AFR exome
AF:
0.0000624
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000146
Gnomad4 OTH exome
AF:
0.0000831
GnomAD4 genome
AF:
0.0000478
AC:
7
AN:
146326
Hom.:
0
Cov.:
24
AF XY:
0.0000419
AC XY:
3
AN XY:
71518
show subpopulations
Gnomad4 AFR
AF:
0.0000552
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000737
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000192
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000124
AC:
15

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 submitterclinical testingAmbry GeneticsAug 19, 2023The c.866C>T (p.T289M) 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 866, causing the threonine (T) at amino acid position 289 to be replaced by a methionine (M). 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
0.069
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
5.5
DANN
Benign
0.85
DEOGEN2
Benign
0.0068
T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.19
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.77
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.47
N;.
REVEL
Benign
0.014
Sift
Benign
0.46
T;.
Sift4G
Benign
0.20
T;.
Polyphen
0.037
B;.
Vest4
0.17
MVP
0.27
ClinPred
0.019
T
GERP RS
-3.4
Varity_R
0.015
gMVP
0.078

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.

Other links and lift over

dbSNP: rs369935801; hg19: chr15-102462397; API