Variant chr14-18601379-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013354.1(OR11H12):c.263A>G(p.Tyr88Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000428 in 1,591,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

OR11H12
NM_001013354.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0950

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055761725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR11H12	NM_001013354.1 linkuse as main transcript	c.263A>G	p.Tyr88Cys	missense_variant	1/1	ENST00000550708.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR11H12	ENST00000550708.2 linkuse as main transcript	c.263A>G	p.Tyr88Cys	missense_variant	1/1		NM_001013354.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000249

AC:

AN:

140446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000701

Gnomad ASJ

AF:

0.000896

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000459

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

217840

Hom.:

AF XY:

0.000227

AC XY:

AN XY:

118770

show subpopulations

Gnomad AFR exome

AF:

0.0000818

Gnomad AMR exome

AF:

0.0000674

Gnomad ASJ exome

AF:

0.000718

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000355

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.000445

AC:

646

AN:

1451000

Hom.:

Cov.:

AF XY:

0.000440

AC XY:

318

AN XY:

722082

show subpopulations

Gnomad4 AFR exome

AF:

0.000154

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.000615

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000550

Gnomad4 OTH exome

AF:

0.000267

GnomAD4 genome

AF:

0.000249

AC:

AN:

140554

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

AN XY:

68486

show subpopulations

Gnomad4 AFR

AF:

0.0000285

Gnomad4 AMR

AF:

0.0000700

Gnomad4 ASJ

AF:

0.000896

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000459

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000290

Hom.:

ESP6500AA

AF:

0.000334

AC:

ESP6500EA

AF:

0.000461

AC:

ExAC

AF:

0.000279

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

Apr 28, 2022

The c.263A>G (p.Y88C) alteration is located in exon 1 (coding exon 1) of the OR11H12 gene. This alteration results from a A to G substitution at nucleotide position 263, causing the tyrosine (Y) at amino acid position 88 to be replaced by a cysteine (C). 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

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.0065

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0029

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-8.9

REVEL

Benign

0.047

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.24

MVP

0.31

MPC

3.5

ClinPred

0.16

GERP RS

0.58

Varity_R

0.63

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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