11-59457567-A-G

Variant summary

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

The NM_001004708.1(OR4D6):ā€‹c.607A>Gā€‹(p.Asn203Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00082 ( 0 hom., cov: 32)
Exomes š‘“: 0.000084 ( 0 hom. )

Consequence

OR4D6
NM_001004708.1 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.595
Variant links:
Genes affected
OR4D6 (HGNC:15175): (olfactory receptor family 4 subfamily D member 6) 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=0.016148686).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR4D6NM_001004708.1 linkuse as main transcriptc.607A>G p.Asn203Asp missense_variant 1/1 ENST00000300127.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR4D6ENST00000300127.3 linkuse as main transcriptc.607A>G p.Asn203Asp missense_variant 1/1 NM_001004708.1 P1

Frequencies

GnomAD3 genomes
AF:
0.000822
AC:
125
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00292
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000223
AC:
56
AN:
251466
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00314
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000841
AC:
123
AN:
1461884
Hom.:
0
Cov.:
36
AF XY:
0.0000701
AC XY:
51
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00317
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000821
AC:
125
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.000753
AC XY:
56
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.00291
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000459
Hom.:
0
Bravo
AF:
0.000963
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000239
AC:
29
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 GeneticsJul 06, 2022The c.607A>G (p.N203D) alteration is located in exon 1 (coding exon 1) of the OR4D6 gene. This alteration results from a A to G substitution at nucleotide position 607, causing the asparagine (N) at amino acid position 203 to be replaced by an aspartic acid (D). 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
-0.49
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0090
T
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.016
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
0.94
N
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.16
Sift
Uncertain
0.024
D
Sift4G
Uncertain
0.032
D
Polyphen
1.0
D
Vest4
0.21
MVP
0.54
MPC
0.33
ClinPred
0.093
T
GERP RS
5.5
Varity_R
0.29
gMVP
0.78

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: rs143011036; hg19: chr11-59225040; API