Variant 14-19713162-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001197287.2(OR11H2):c.722C>T(p.Ala241Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0013 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

OR11H2
NM_001197287.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

OR11H2 (HGNC:14716): (olfactory receptor family 11 subfamily H member 2) 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]

OR11H2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0696238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR11H2	NM_001197287.2 linkuse as main transcript	c.722C>T	p.Ala241Val	missense_variant	1/1	ENST00000556246.3	NP_001184216.2	Q8NH07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR11H2	ENST00000556246.3 linkuse as main transcript	c.722C>T	p.Ala241Val	missense_variant	1/1	6	NM_001197287.2	ENSP00000485150.2		A0A2C9F2Y1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

103

AN:

144956

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000342

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000679

Gnomad FIN

AF:

0.000705

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.000504

GnomAD3 exomes

AF:

0.000184

AC:

AN:

228632

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

123128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000375

Gnomad FIN exome

AF:

0.000152

Gnomad NFE exome

AF:

0.000302

Gnomad OTH exome

AF:

0.000350

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00134

AC:

1946

AN:

1448538

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

916

AN XY:

721114

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000919

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000361

Gnomad4 FIN exome

AF:

0.000619

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000710

AC:

103

AN:

145072

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

70614

show subpopulations

Gnomad4 AFR

AF:

0.000154

Gnomad4 AMR

AF:

0.000341

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000680

Gnomad4 FIN

AF:

0.000705

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.000499

Alfa

AF:

0.000514

Hom.:

ExAC

AF:

0.000153

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

Aug 02, 2021

The c.755C>T (p.A252V) alteration is located in exon 2 (coding exon 1) of the OR11H2 gene. This alteration results from a C to T substitution at nucleotide position 755, causing the alanine (A) at amino acid position 252 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.020

T;.

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.070

T;T

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Benign

0.25

MVP

0.16

GERP RS

1.3

Varity_R

0.030

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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