Variant chr11-55603876-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001004700.3(OR4C11):c.498C>A(p.Phe166Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000517 in 1,353,620 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000052 ( 2 hom. )

Consequence

OR4C11
NM_001004700.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.715

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31644726).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4C11	NM_001004700.3 linkuse as main transcript	c.498C>A	p.Phe166Leu	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.498C>A	p.Phe166Leu	missense_variant	4/4		NM_001004700.3	ENSP00000492971.1		Q6IEV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000877

AC:

AN:

228024

Hom.:

AF XY:

0.00000809

AC XY:

AN XY:

123572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000128

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000517

AC:

AN:

1353620

Hom.:

Cov.:

AF XY:

0.00000594

AC XY:

AN XY:

673412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000289

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000193

Gnomad4 OTH exome

AF:

0.0000715

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000176

AC:

Asia WGS

AF:

0.00161

AC:

AN:

3120

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

Oct 10, 2023

The c.498C>A (p.F166L) alteration is located in exon 1 (coding exon 1) of the OR4C11 gene. This alteration results from a C to A substitution at nucleotide position 498, causing the phenylalanine (F) at amino acid position 166 to be replaced by a leucine (L). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0057

T;T

Eigen

Benign

0.10

Eigen_PC

Benign

-0.077

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.00077

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-5.7

.;D

REVEL

Benign

0.11

Sift

Uncertain

0.013

.;D

Sift4G

Uncertain

0.016

.;D

Polyphen

1.0

D;D

Vest4

0.14

MutPred

0.44

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);

MVP

0.55

MPC

0.0062

ClinPred

0.84

GERP RS

3.4

Varity_R

0.53

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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