Genetic Variant NM_153444.1:c.233T>C (chr11-7796710-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_153444.1(OR5P2):c.233T>C(p.Leu78Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000685 in 1,605,578 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 5 hom. )

Consequence

OR5P2
NM_153444.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Publications

1 publications found

Variant links:

Genes affected

OR5P2 (HGNC:14783): (olfactory receptor family 5 subfamily P 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]

OR5P2 links:

ENSG00000271758 (HGNC:):

ENSG00000271758 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.909

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153444.1. 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
	OR5P2	NM_153444.1	MANE Select	c.233T>C	p.Leu78Pro	missense	Exon 1 of 1	NP_703145.1	A0A126GVJ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR5P2	ENST00000329434.3	TSL:6 MANE Select	c.233T>C	p.Leu78Pro	missense	Exon 1 of 1	ENSP00000331823.2	Q8WZ92
ENSG00000271758	ENST00000527565.1	TSL:3	n.542+82297T>C		intron	N/A
ENSG00000254951	ENST00000529488.5	TSL:5	n.532-42189T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000675

AC:

AN:

148098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000133

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000561

AC:

AN:

249568

AF XY:

0.0000593

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000686

AC:

100

AN:

1457480

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

725132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31564

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39298

South Asian (SAS)

AF:

0.00

AC:

AN:

85702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000900

AC:

100

AN:

1110868

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000675

AC:

AN:

148098

Hom.:

Cov.:

AF XY:

0.0000691

AC XY:

AN XY:

72308

show subpopulations

African (AFR)

AF:

0.0000263

AC:

AN:

37978

American (AMR)

AF:

0.00

AC:

AN:

15110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00

AC:

AN:

4698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000671

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

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

Uncertain

0.38

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.0

PhyloP100

5.9

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.90

MVP

0.56

MPC

0.022

ClinPred

0.99

GERP RS

5.5

PromoterAI

-0.0031

Neutral

(source)

Varity_R

0.98

gMVP

0.56

Mutation Taster

=92/8

polymorphism

(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