Genetic Variant OGFR:p.Arg244Pro (chr20-62812346-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007346.4(OGFR):c.731G>C(p.Arg244Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,564,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R244Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

OGFR
NM_007346.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.876

Publications

1 publications found

Variant links:

Genes affected

OGFR (HGNC:15768): (opioid growth factor receptor) The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported. [provided by RefSeq, Jul 2008]

OGFR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGFR	NM_007346.4 link	c.731G>C	p.Arg244Pro	missense_variant	Exon 7 of 7	ENST00000290291.10	NP_031372.2	Q9NZT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGFR	ENST00000290291.10 link	c.731G>C	p.Arg244Pro	missense_variant	Exon 7 of 7	1	NM_007346.4	ENSP00000290291.6		Q9NZT2-1
OGFR	ENST00000370461.5 link	c.575G>C	p.Arg192Pro	missense_variant	Exon 5 of 5	2		ENSP00000359491.1		A0A0A0MRN5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412552

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698638

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32144

American (AMR)

AF:

0.00

AC:

AN:

37792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25312

East Asian (EAS)

AF:

0.00

AC:

AN:

36612

South Asian (SAS)

AF:

0.00

AC:

AN:

80776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087304

Other (OTH)

AF:

0.00

AC:

AN:

58482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.60

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.021

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.97

L;.;.

PhyloP100

0.88

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;.;N

REVEL

Benign

0.057

Sift

Benign

0.076

T;.;D

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0080

B;.;.

Vest4

0.27

MutPred

0.47

Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);.;

MVP

0.10

MPC

0.41

ClinPred

0.087

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.71

Mutation Taster

=89/11

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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chr20-62812346-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over