Variant 11-55603972-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001004700.3(OR4C11):c.402G>A(p.Met134Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,490,230 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00014 ( 39 hom. )

Consequence

OR4C11
NM_001004700.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

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]

OR4C11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23413849).

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4C11	NM_001004700.3 linkuse as main transcript	c.402G>A	p.Met134Ile	missense_variant	4/4	ENST00000641580.1	NP_001004700.2	Q6IEV9A0A126GVN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4C11	ENST00000641580.1 linkuse as main transcript	c.402G>A	p.Met134Ile	missense_variant	4/4		NM_001004700.3	ENSP00000492971.1		Q6IEV9

Frequencies

GnomAD3 genomes

AF:

0.0000362

AC:

AN:

138182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000237

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:

0.0000322

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000978

AC:

AN:

224884

Hom.:

AF XY:

0.0000902

AC XY:

AN XY:

121898

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000524

Gnomad NFE exome

AF:

0.000125

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.000138

AC:

187

AN:

1352048

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

672506

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000272

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000625

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.000161

GnomAD4 genome

AF:

0.0000362

AC:

AN:

138182

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

66992

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000237

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000322

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000618

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.402G>A (p.M134I) 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 402, causing the methionine (M) at amino acid position 134 to be replaced by an isoleucine (I). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.00084

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

.;D

REVEL

Benign

0.15

Sift

Uncertain

0.027

.;D

Sift4G

Uncertain

0.023

.;D

Polyphen

1.0

D;D

Vest4

0.27

MutPred

0.43

Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);

MVP

0.57

MPC

0.0039

ClinPred

0.59

GERP RS

3.4

Varity_R

0.54

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over