Genetic Variant OR11H12:p.Thr49Ile (chr14-18601262-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013354.1(OR11H12):c.146C>T(p.Thr49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,604,654 control chromosomes in the GnomAD database, including 13 homozygotes. 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 0.0016 ( 7 hom., cov: 20)

Exomes 𝑓: 0.00018 ( 6 hom. )

Consequence

OR11H12
NM_001013354.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0760

Publications

2 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028055519).

BS2

High Homozygotes in GnomAd4 at 7 gene

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.146C>T	p.Thr49Ile	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.146C>T	p.Thr49Ile	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
ENSG00000306587	ENST00000819518.1		n.114+11205C>T		intron	N/A
ENSG00000306587	ENST00000819519.1		n.188+1487C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

232

AN:

145688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000546

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:

0.000134

Gnomad OTH

AF:

0.00152

GnomAD2 exomes

AF:

0.0000923

AC:

AN:

249220

AF XY:

0.0000518

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000179

AC:

261

AN:

1458850

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

113

AN XY:

725812

show subpopulations

African (AFR)

AF:

0.00374

AC:

124

AN:

33120

American (AMR)

AF:

0.000470

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.000126

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.000485

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.0000621

AC:

AN:

1111372

Other (OTH)

AF:

0.000648

AC:

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00159

AC:

232

AN:

145804

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

112

AN XY:

71088

show subpopulations

African (AFR)

AF:

0.00562

AC:

212

AN:

37690

American (AMR)

AF:

0.000545

AC:

AN:

14682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

4978

South Asian (SAS)

AF:

0.00

AC:

AN:

4648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000135

AC:

AN:

66908

Other (OTH)

AF:

0.00150

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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.:

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

0.071

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.4

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.000030

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00060

LIST_S2

Benign

0.074

M_CAP

Benign

0.0058

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

PhyloP100

-0.076

PrimateAI

Benign

0.28

PROVEAN

Benign

1.4

REVEL

Benign

0.029

Sift

Benign

0.77

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.040

MVP

0.22

MPC

1.8

ClinPred

0.011

PromoterAI

-0.0058

Neutral

(source)

Varity_R

0.041

gMVP

0.038

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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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