11-55603446-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004700.3(OR4C11):​c.928G>A​(p.Gly310Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000655 in 1,389,418 control chromosomes in the GnomAD database, including 18 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 25)
Exomes 𝑓: 0.000071 ( 18 hom. )

Consequence

OR4C11
NM_001004700.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.459
Variant links:
Genes affected
OR4C11 (HGNC:15167): (olfactory receptor family 4 subfamily C member 11) 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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.021000057).
BS2
High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4C11NM_001004700.3 linkuse as main transcriptc.928G>A p.Gly310Arg missense_variant 4/4 ENST00000641580.1 NP_001004700.2 Q6IEV9A0A126GVN6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4C11ENST00000641580.1 linkuse as main transcriptc.928G>A p.Gly310Arg missense_variant 4/4 NM_001004700.3 ENSP00000492971.1 Q6IEV9

Frequencies

GnomAD3 genomes
AF:
0.0000145
AC:
2
AN:
137930
Hom.:
0
Cov.:
25
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000473
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000878
AC:
17
AN:
193678
Hom.:
1
AF XY:
0.000144
AC XY:
15
AN XY:
104388
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:
0.000786
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000711
AC:
89
AN:
1251488
Hom.:
18
Cov.:
25
AF XY:
0.000103
AC XY:
64
AN XY:
622976
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:
0.00110
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000104
Gnomad4 OTH exome
AF:
0.000153
GnomAD4 genome
AF:
0.0000145
AC:
2
AN:
137930
Hom.:
0
Cov.:
25
AF XY:
0.0000150
AC XY:
1
AN XY:
66804
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000473
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.000108
AC:
12
Asia WGS
AF:
0.00321
AC:
10
AN:
3124

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 GeneticsSep 16, 2021The c.928G>A (p.G310R) alteration is located in exon 1 (coding exon 1) of the OR4C11 gene. This alteration results from a G to A substitution at nucleotide position 928, causing the glycine (G) at amino acid position 310 to be replaced by an arginine (R). 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
-0.60
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.00049
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.00071
N
LIST_S2
Benign
0.34
.;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.021
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.85
.;N
REVEL
Benign
0.0080
Sift
Uncertain
0.0050
.;D
Sift4G
Pathogenic
0.0
.;D
Polyphen
0.0
B;B
Vest4
0.077
MutPred
0.38
Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP
0.014
MPC
0.0030
ClinPred
0.057
T
GERP RS
-6.4
Varity_R
0.070
gMVP
0.068

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: rs772341211; hg19: chr11-55370922; COSMIC: COSV56354418; API