chr11-4640520-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004751.3(OR51D1):​c.730C>T​(p.Arg244Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R244R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

OR51D1
NM_001004751.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.965
Variant links:
Genes affected
OR51D1 (HGNC:15193): (olfactory receptor family 51 subfamily D member 1) 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=0.05534494).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR51D1NM_001004751.3 linkuse as main transcriptc.730C>T p.Arg244Trp missense_variant 2/2 ENST00000641817.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR51D1ENST00000641817.1 linkuse as main transcriptc.730C>T p.Arg244Trp missense_variant 2/2 NM_001004751.3 P1
OR51D1ENST00000357605.2 linkuse as main transcriptc.730C>T p.Arg244Trp missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151964
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251288
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000766
AC:
112
AN:
1461744
Hom.:
0
Cov.:
35
AF XY:
0.0000908
AC XY:
66
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000908
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151964
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74178
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 GeneticsApr 30, 2024The c.730C>T (p.R244W) alteration is located in exon 1 (coding exon 1) of the OR51D1 gene. This alteration results from a C to T substitution at nucleotide position 730, causing the arginine (R) at amino acid position 244 to be replaced by a tryptophan (W). 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
0.13
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.4
DANN
Benign
0.56
DEOGEN2
Benign
0.013
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.099
.;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.055
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.20
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Benign
0.011
Sift
Benign
0.099
.;T
Sift4G
Benign
0.078
.;T
Polyphen
0.0010
B;B
Vest4
0.16
MutPred
0.36
Loss of glycosylation at S243 (P = 0.0297);Loss of glycosylation at S243 (P = 0.0297);
MVP
0.15
MPC
0.011
ClinPred
0.018
T
GERP RS
-2.4
Varity_R
0.064
gMVP
0.18

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: rs138670452; hg19: chr11-4661750; COSMIC: COSV100712333; COSMIC: COSV100712333; API