5-180739959-A-C

Variant summary

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

The NM_001001657.1(OR2Y1):ā€‹c.100T>Gā€‹(p.Phe34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,832 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

OR2Y1
NM_001001657.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.117
Variant links:
Genes affected
OR2Y1 (HGNC:14837): (olfactory receptor family 2 subfamily Y 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=0.049001336).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2Y1NM_001001657.1 linkuse as main transcriptc.100T>G p.Phe34Val missense_variant 1/1 ENST00000307832.3 NP_001001657.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2Y1ENST00000307832.3 linkuse as main transcriptc.100T>G p.Phe34Val missense_variant 1/1 NM_001001657.1 ENSP00000312403 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251392
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135888
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:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461832
Hom.:
0
Cov.:
35
AF XY:
0.0000248
AC XY:
18
AN XY:
727216
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:
0.000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000330
AC:
4

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 GeneticsNov 09, 2021The c.100T>G (p.F34V) alteration is located in exon 1 (coding exon 1) of the OR2Y1 gene. This alteration results from a T to G substitution at nucleotide position 100, causing the phenylalanine (F) at amino acid position 34 to be replaced by a valine (V). 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
-0.46
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
18
DANN
Benign
0.70
DEOGEN2
Benign
0.025
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.85
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.21
T
PROVEAN
Uncertain
-4.1
D
REVEL
Benign
0.068
Sift
Benign
0.072
T
Sift4G
Benign
0.33
T
Polyphen
0.042
B
Vest4
0.14
MutPred
0.29
Gain of catalytic residue at F34 (P = 0.1978);
MVP
0.25
MPC
0.18
ClinPred
0.070
T
GERP RS
3.2
Varity_R
0.47
gMVP
0.20

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: rs746077912; hg19: chr5-180166959; API