Genetic Variant NM_001013354.1:c.202T>C (chr14-18601318-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 14/20 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

Publications

6 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 -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 VariationId is 2644024.Status of the report is criteria_provided_single_submitter, 1 stars.

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.202T>C	p.Trp68Arg	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.202T>C	p.Trp68Arg	missense	Exon 1 of 1	ENSP00000449002.1	B2RN74
ENSG00000306587	ENST00000819518.1		n.114+11261T>C		intron	N/A
ENSG00000306587	ENST00000819519.1		n.188+1543T>C		intron	N/A

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

GnomAD2 exomes

AF:

0.000587

AC:

132

AN:

224770

AF XY:

0.000484

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 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

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

African (AFR)

AF:

0.0373

AC:

1008

AN:

27036

American (AMR)

AF:

0.0134

AC:

544

AN:

40514

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

533

AN:

23162

East Asian (EAS)

AF:

0.0283

AC:

1011

AN:

35712

South Asian (SAS)

AF:

0.0196

AC:

1570

AN:

80120

European-Finnish (FIN)

AF:

0.0249

AC:

1198

AN:

48124

Middle Eastern (MID)

AF:

0.0317

AC:

112

AN:

3536

European-Non Finnish (NFE)

AF:

0.0104

AC:

10475

AN:

1005772

Other (OTH)

AF:

0.0207

AC:

1100

AN:

53240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

128

257

385

514

642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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

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

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

African (AFR)

AF:

0.00929

AC:

237

AN:

25518

American (AMR)

AF:

0.00890

AC:

101

AN:

11344

Ashkenazi Jewish (ASJ)

AF:

0.00770

AC:

AN:

2726

East Asian (EAS)

AF:

0.0170

AC:

AN:

3834

South Asian (SAS)

AF:

0.00928

AC:

AN:

3556

European-Finnish (FIN)

AF:

0.00967

AC:

AN:

8068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.00786

AC:

403

AN:

51302

Other (OTH)

AF:

0.00748

AC:

AN:

1470

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.257

Heterozygous variant carriers

127

254

381

508

635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0140

Hom.:

100

ExAC

AF:

0.0000772

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.63

(source)

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

PhyloP100

-2.5

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

PromoterAI

-0.0046

Neutral

(source)

Varity_R

0.029

gMVP

0.020

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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