Variant 11-55603767-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001004700.3(OR4C11):c.607G>T(p.Ala203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,488,706 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 6 hom., cov: 25)

Exomes 𝑓: 0.00038 ( 119 hom. )

Consequence

OR4C11
NM_001004700.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.93

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016928613).

BP6

Variant 11-55603767-C-A is Benign according to our data. Variant chr11-55603767-C-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4C11	NM_001004700.3 linkuse as main transcript	c.607G>T	p.Ala203Ser	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.607G>T	p.Ala203Ser	missense_variant	4/4		NM_001004700.3	ENSP00000492971.1		Q6IEV9

Frequencies

GnomAD3 genomes

AF:

0.000268

AC:

AN:

138014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000755

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000531

Gnomad OTH

AF:

0.000541

GnomAD3 exomes

AF:

0.000445

AC:

101

AN:

226858

Hom.:

AF XY:

0.000333

AC XY:

AN XY:

122960

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000104

Gnomad NFE exome

AF:

0.000921

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000377

AC:

509

AN:

1350604

Hom.:

119

Cov.:

AF XY:

0.000318

AC XY:

214

AN XY:

671984

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.0000806

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000291

Gnomad4 NFE exome

AF:

0.000421

Gnomad4 OTH exome

AF:

0.000931

GnomAD4 genome

AF:

0.000268

AC:

AN:

138102

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

67020

show subpopulations

Gnomad4 AFR

AF:

0.0000752

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000531

Gnomad4 OTH

AF:

0.000541

Alfa

AF:

0.000164

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000374

AC:

ExAC

AF:

0.000793

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

Aug 20, 2024

The c.607G>T (p.A203S) alteration is located in exon 1 (coding exon 1) of the OR4C11 gene. This alteration results from a G to T substitution at nucleotide position 607, causing the alanine (A) at amino acid position 203 to be replaced by a serine (S). 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

-0.50

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0051

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.00080

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.051

Sift

Benign

0.21

.;T

Sift4G

Benign

0.36

.;T

Polyphen

0.043

B;B

Vest4

0.045

MVP

0.13

MPC

0.0036

ClinPred

0.014

GERP RS

1.4

Varity_R

0.10

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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