Genetic Variant OR5H2:c.-11C>T (chr3-98282892-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005482.2(OR5H2):c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,611,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

OR5H2
NM_001005482.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.806

Publications

4 publications found

Variant links:

Genes affected

OR5H2 (HGNC:14752): (olfactory receptor family 5 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]

OR5H2 links:

ENSG00000251088 (HGNC:):

ENSG00000251088 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024447918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005482.2. 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
	OR5H2	NM_001005482.2	MANE Select	c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_001005482.2	Q8NGV7
	OR5H2	NM_001005482.2	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 1	NP_001005482.2	Q8NGV7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OR5H2	ENST00000355273.3	TSL:6 MANE Select	c.-11C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000347418.3	Q8NGV7
OR5H2	ENST00000355273.3	TSL:6 MANE Select	c.-11C>T	5_prime_UTR	Exon 1 of 1	ENSP00000347418.3	Q8NGV7
ENSG00000251088	ENST00000508616.1	TSL:1	n.27-28994C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000168

AC:

AN:

250086

AF XY:

0.0000814

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000497

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1459750

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

726202

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33412

American (AMR)

AF:

0.000496

AC:

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1110808

Other (OTH)

AF:

0.0000829

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000598

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41522

American (AMR)

AF:

0.000327

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000194

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

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

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.6

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.43

M_CAP

Benign

0.0022

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.0

PhyloP100

-0.81

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.68

REVEL

Benign

0.037

Sift

Benign

0.044

Sift4G

Uncertain

0.033

Polyphen

0.89

Vest4

0.084

MVP

0.24

MPC

0.025

ClinPred

0.013

GERP RS

-2.5

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.036

gMVP

0.21

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

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