15-101818248-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001001674.2(OR4F15):​c.62G>A​(p.Arg21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,613,838 control chromosomes in the GnomAD database, including 29 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 25 hom. )

Consequence

OR4F15
NM_001001674.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.476
Variant links:
Genes affected
OR4F15 (HGNC:15078): (olfactory receptor family 4 subfamily F member 15) 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 Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004750639).
BP6
Variant 15-101818248-G-A is Benign according to our data. Variant chr15-101818248-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645760.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00399 (5837/1461662) while in subpopulation MID AF= 0.0299 (172/5760). AF 95% confidence interval is 0.0262. There are 25 homozygotes in gnomad4_exome. There are 2944 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4F15NM_001001674.2 linkuse as main transcriptc.62G>A p.Arg21Gln missense_variant 2/2 ENST00000332238.5 NP_001001674.1 Q8NGB8A0A126GW41

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4F15ENST00000332238.5 linkuse as main transcriptc.62G>A p.Arg21Gln missense_variant 2/26 NM_001001674.2 ENSP00000333184.4 Q8NGB8

Frequencies

GnomAD3 genomes
AF:
0.00359
AC:
546
AN:
152058
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000869
Gnomad AMI
AF:
0.0505
Gnomad AMR
AF:
0.00380
Gnomad ASJ
AF:
0.0118
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00500
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00344
AC:
864
AN:
251020
Hom.:
3
AF XY:
0.00371
AC XY:
503
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00350
Gnomad ASJ exome
AF:
0.00845
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00490
Gnomad OTH exome
AF:
0.00801
GnomAD4 exome
AF:
0.00399
AC:
5837
AN:
1461662
Hom.:
25
Cov.:
31
AF XY:
0.00405
AC XY:
2944
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.00182
Gnomad4 AMR exome
AF:
0.00369
Gnomad4 ASJ exome
AF:
0.00892
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00162
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.00427
Gnomad4 OTH exome
AF:
0.00523
GnomAD4 genome
AF:
0.00358
AC:
545
AN:
152176
Hom.:
4
Cov.:
32
AF XY:
0.00331
AC XY:
246
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.000867
Gnomad4 AMR
AF:
0.00379
Gnomad4 ASJ
AF:
0.0118
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00125
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00500
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00514
Hom.:
10
Bravo
AF:
0.00430
TwinsUK
AF:
0.00351
AC:
13
ALSPAC
AF:
0.00337
AC:
13
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00535
AC:
46
ExAC
AF:
0.00335
AC:
407
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00616
EpiControl
AF:
0.00646

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023OR4F15: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.00096
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.20
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.0048
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.020
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.12
N
REVEL
Benign
0.13
Sift
Benign
0.14
T
Sift4G
Benign
0.58
T
Polyphen
0.0
B
Vest4
0.17
MVP
0.31
MPC
0.011
ClinPred
0.0051
T
GERP RS
4.4
Varity_R
0.045
gMVP
0.032

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.

Other links and lift over

dbSNP: rs142759394; hg19: chr15-102358451; API