Genetic Variant OR11H12:p.Trp68Arg (chr14-18601318-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001013354.1(OR11H12):c.202T>C(p.Trp68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 3 hom., cov: 20)

Exomes 𝑓: 0.013 ( 7992 hom. )

Failed GnomAD Quality Control

Consequence

OR11H12
NM_001013354.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48

Variant links:

Genes affected

OR11H12 (HGNC:30738): (olfactory receptor family 11 subfamily H member 12) 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]

OR11H12 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=0.0036748946).

BP6

Variant 14-18601318-T-C is Benign according to our data. Variant chr14-18601318-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644024.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR11H12	NM_001013354.1 link	c.202T>C	p.Trp68Arg	missense_variant	Exon 1 of 1	ENST00000550708.2	NP_001013372.1	B2RN74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR11H12	ENST00000550708.2 link	c.202T>C	p.Trp68Arg	missense_variant	Exon 1 of 1	6	NM_001013354.1	ENSP00000449002.1		B2RN74

Frequencies

GnomAD3 genomes

AF:

0.00877

AC:

954

AN:

108746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00931

Gnomad AMI

AF:

0.00391

Gnomad AMR

AF:

0.00891

Gnomad ASJ

AF:

0.00770

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.00926

Gnomad FIN

AF:

0.00967

Gnomad MID

AF:

0.00435

Gnomad NFE

AF:

0.00785

Gnomad OTH

AF:

0.00757

GnomAD3 exomes

AF:

0.000587

AC:

132

AN:

224770

Hom.:

AF XY:

0.000484

AC XY:

AN XY:

122002

show subpopulations

Gnomad AFR exome

AF:

0.00187

Gnomad AMR exome

AF:

0.000708

Gnomad ASJ exome

AF:

0.000338

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.000143

Gnomad FIN exome

AF:

0.000197

Gnomad NFE exome

AF:

0.000428

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0133

AC:

17551

AN:

1317216

Hom.:

7992

Cov.:

AF XY:

0.0142

AC XY:

9291

AN XY:

655622

show subpopulations

Gnomad4 AFR exome

AF:

0.0373

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0230

Gnomad4 EAS exome

AF:

0.0283

Gnomad4 SAS exome

AF:

0.0196

Gnomad4 FIN exome

AF:

0.0249

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00875

AC:

952

AN:

108806

Hom.:

Cov.:

AF XY:

0.00851

AC XY:

454

AN XY:

53328

show subpopulations

Gnomad4 AFR

AF:

0.00929

Gnomad4 AMR

AF:

0.00890

Gnomad4 ASJ

AF:

0.00770

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.00928

Gnomad4 FIN

AF:

0.00967

Gnomad4 NFE

AF:

0.00786

Gnomad4 OTH

AF:

0.00748

Alfa

AF:

0.0140

Hom.:

100

ExAC

AF:

0.0000772

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR11H12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.63

DANN

Benign

0.25

DEOGEN2

Benign

0.00027

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00061

LIST_S2

Benign

0.012

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.1

PrimateAI

Benign

0.26

PROVEAN

Benign

2.7

REVEL

Benign

0.057

Sift

Benign

0.47

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.022

MutPred

0.32

Gain of catalytic residue at T72 (P = 2e-04);

MVP

0.093

MPC

2.5

ClinPred

0.0023

GERP RS

-1.2

Varity_R

0.029

gMVP

0.020

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