Genetic Variant OR11H12:p.Gln30Glu (chr14-18601204-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013354.1(OR11H12):c.88C>G(p.Gln30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,608,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR11H12
NM_001013354.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.70

Publications

1 publications found

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:

ENSG00000306587 (HGNC:):

ENSG00000306587 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05397916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013354.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR11H12	NM_001013354.1	MANE Select	c.88C>G	p.Gln30Glu	missense	Exon 1 of 1	NP_001013372.1	B2RN74

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR11H12	ENST00000550708.2	TSL:6 MANE Select	c.88C>G	p.Gln30Glu	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
ENSG00000306587	ENST00000819518.1		n.114+11147C>G		intron	N/A
ENSG00000306587	ENST00000819519.1		n.188+1429C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149358

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000667

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

250044

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000254

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000206

AC:

AN:

1459510

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726066

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000600

AC:

AN:

33318

American (AMR)

AF:

0.0000224

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111764

Other (OTH)

AF:

0.00

AC:

AN:

60192

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00109982), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149358

Hom.:

Cov.:

AF XY:

0.0000412

AC XY:

AN XY:

72836

show subpopulations

African (AFR)

AF:

0.0000505

AC:

AN:

39576

American (AMR)

AF:

0.0000667

AC:

AN:

14992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67732

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.4

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0051

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0080

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.015

PhyloP100

-1.7

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.95

REVEL

Benign

0.020

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.20

Vest4

0.029

MVP

0.25

MPC

1.8

ClinPred

0.036

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.17

gMVP

0.017

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over