Variant 6-29462611-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030883.5(OR2H1):c.842C>G(p.Pro281Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000802 in 1,613,034 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 4 hom. )

Consequence

OR2H1
NM_030883.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.66

Variant links:

Genes affected

OR2H1 (HGNC:8252): (olfactory receptor family 2 subfamily H member 1) 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]

OR2H1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018716544).

BP6

Variant 6-29462611-C-G is Benign according to our data. Variant chr6-29462611-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656321.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2H1	NM_030883.5 linkuse as main transcript	c.842C>G	p.Pro281Arg	missense_variant	4/4	ENST00000377133.6	NP_112145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2H1	ENST00000377133.6 linkuse as main transcript	c.842C>G	p.Pro281Arg	missense_variant	4/4		NM_030883.5	ENSP00000366337	P1

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

375

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00794

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000950

AC:

234

AN:

246412

Hom.:

AF XY:

0.00101

AC XY:

136

AN XY:

134272

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00148

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000489

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000628

AC:

918

AN:

1460748

Hom.:

Cov.:

AF XY:

0.000669

AC XY:

486

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.00860

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000352

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.00246

AC:

375

AN:

152286

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00792

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000635

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00464

AC:

ESP6500EA

AF:

0.000185

AC:

ExAC

AF:

0.00107

AC:

126

EpiCase

AF:

0.000545

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

OR2H1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;T;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.97

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

H;H;H;H

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-8.7

D;D;D;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.71

MVP

0.50

MPC

0.32

ClinPred

0.13

GERP RS

3.1

Varity_R

0.55

gMVP

0.34

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

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