11-48264189-C-T

Variant summary

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

The NM_001004726.1(OR4X1):​c.329C>T​(p.Ala110Val) 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. 15/21 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. A110D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

OR4X1
NM_001004726.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.318
Variant links:
Genes affected
OR4X1 (HGNC:14854): (olfactory receptor family 4 subfamily X 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

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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=0.034608483).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4X1NM_001004726.1 linkc.329C>T p.Ala110Val missense_variant Exon 1 of 1 ENST00000320048.1 NP_001004726.1 Q8NH49

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4X1ENST00000320048.1 linkc.329C>T p.Ala110Val missense_variant Exon 1 of 1 6 NM_001004726.1 ENSP00000321506.1 Q8NH49

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
11
DANN
Benign
0.90
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.035
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.5
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
3.4
N
REVEL
Benign
0.040
Sift
Benign
0.38
T
Sift4G
Benign
0.46
T
Polyphen
0.0010
B
Vest4
0.079
MutPred
0.34
Gain of catalytic residue at A110 (P = 0.4759);
MVP
0.25
MPC
0.0024
ClinPred
0.059
T
GERP RS
3.1
Varity_R
0.038
gMVP
0.030

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1217872034; hg19: chr11-48285741; API