11-4449796-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001005172.2(OR52K2):​c.457C>T​(p.Arg153Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

OR52K2
NM_001005172.2 missense

Scores

2
2
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.75
Variant links:
Genes affected
OR52K2 (HGNC:15223): (olfactory receptor family 52 subfamily K member 2) 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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.092983514).
BP6
Variant 11-4449796-C-T is Benign according to our data. Variant chr11-4449796-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3411626.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR52K2NM_001005172.2 linkc.457C>T p.Arg153Trp missense_variant Exon 1 of 1 ENST00000325719.4 NP_001005172.2 Q8NGK3A0A126GVK8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR52K2ENST00000325719.4 linkc.457C>T p.Arg153Trp missense_variant Exon 1 of 1 6 NM_001005172.2 ENSP00000318956.4 Q8NGK3

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251172
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000617
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461854
Hom.:
0
Cov.:
32
AF XY:
0.0000303
AC XY:
22
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000494
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Benign:1
Nov 23, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.0072
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.093
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Pathogenic
3.6
H
PrimateAI
Benign
0.20
T
PROVEAN
Pathogenic
-7.3
D
REVEL
Benign
0.072
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.015
D
Polyphen
0.032
B
Vest4
0.16
MVP
0.11
MPC
0.0040
ClinPred
0.25
T
GERP RS
2.1
Varity_R
0.41
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs143862015; hg19: chr11-4471026; COSMIC: COSV57835147; API