Variant 11-124015645-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001004462.2(OR10G4):c.71T>C(p.Leu24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,060 control chromosomes in the GnomAD database, including 5,394 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 5394 hom., cov: 30)

Exomes 𝑓: 0.25 ( 62709 hom. )

Failed GnomAD Quality Control

Consequence

OR10G4
NM_001004462.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.426

Variant links:

Genes affected

OR10G4 (HGNC:14809): (olfactory receptor family 10 subfamily G member 4) 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]

OR10G4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003057152).

BP6

Variant 11-124015645-T-C is Benign according to our data. Variant chr11-124015645-T-C is described in ClinVar as [Benign]. Clinvar id is 2796335.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10G4	NM_001004462.2 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant	2/2	ENST00000641722.1	NP_001004462.1	Q8NGN3A0A126GWS5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10G4	ENST00000641722.1 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant	2/2		NM_001004462.2	ENSP00000493036.1		Q8NGN3
OR10G4	ENST00000641521.1 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant	3/3			ENSP00000493354.1		Q8NGN3

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36664

AN:

150944

Hom.:

5395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.126

AC:

26241

AN:

207902

Hom.:

6452

AF XY:

0.120

AC XY:

13481

AN XY:

112474

show subpopulations

Gnomad AFR exome

AF:

0.0410

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.0604

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.0774

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.249

AC:

313777

AN:

1261048

Hom.:

62709

Cov.:

AF XY:

0.243

AC XY:

153323

AN XY:

629876

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.243

AC:

36684

AN:

151060

Hom.:

5394

Cov.:

AF XY:

0.247

AC XY:

18223

AN XY:

73720

show subpopulations

Gnomad4 AFR

AF:

0.0908

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.335

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.223

Hom.:

945

Bravo

AF:

0.234

ExAC

AF:

0.171

AC:

20682

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.9

DANN

Benign

0.094

DEOGEN2

Benign

0.0071

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.0038

.;.;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.72

N;N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.0

.;.;N

REVEL

Benign

0.047

Sift

Benign

0.55

.;.;T

Sift4G

Benign

0.46

.;.;T

Polyphen

0.0

B;B;B

Vest4

0.062

MPC

0.76

ClinPred

0.0031

GERP RS

-2.7

Varity_R

0.20

gMVP

0.57

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.

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