7-144258886-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005328.2(OR2A7):​c.743G>A​(p.Gly248Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G248V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR2A7
NM_001005328.2 missense

Scores

1
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.666
Variant links:
Genes affected
OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A member 7) 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]
ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)
OR2A1-AS1 (HGNC:49168): (OR2A1 antisense RNA 1)
ARHGEF34P (HGNC:38086): (Rho guanine nucleotide exchange factor 34, pseudogene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2606038).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR2A7NM_001005328.2 linkc.743G>A p.Gly248Glu missense_variant Exon 2 of 2 ENST00000641841.1 NP_001005328.1 Q96R45A0A126GWD8
ARHGEF35-AS1NR_126022.1 linkn.494-21586C>T intron_variant Intron 2 of 4
OR2A1-AS1NR_126023.1 linkn.608-19143G>A intron_variant Intron 3 of 4
ARHGEF34PNR_033942.1 linkn.*110G>A downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR2A7ENST00000641841.1 linkc.743G>A p.Gly248Glu missense_variant Exon 2 of 2 NM_001005328.2 ENSP00000493320.1 Q96R45

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461534
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727076
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.033
T;T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.067
N
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-5.1
.;D
REVEL
Benign
0.14
Sift
Benign
0.038
.;D
Sift4G
Benign
0.34
.;T
Polyphen
0.86
P;P
Vest4
0.44
MutPred
0.61
Loss of catalytic residue at L249 (P = 0.1137);Loss of catalytic residue at L249 (P = 0.1137);
MVP
0.42
ClinPred
0.77
D
GERP RS
2.3
Varity_R
0.45
gMVP
0.13

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: rs757342704; hg19: chr7-143955979; API