Genetic Variant OGFR:p.Ser324Arg (chr20-62812587-C-G) – 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_007346.4(OGFR):c.972C>G(p.Ser324Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,571,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

OGFR
NM_007346.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.967

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054689318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGFR	NM_007346.4 link	c.972C>G	p.Ser324Arg	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.972C>G	p.Ser324Arg	missense_variant	Exon 7 of 7	1	NM_007346.4	ENSP00000290291.6		Q9NZT2-1
OGFR	ENST00000370461.5 link	c.816C>G	p.Ser272Arg	missense_variant	Exon 5 of 5	2		ENSP00000359491.1		A0A0A0MRN5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

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:

0.000956

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

173470

AF XY:

0.0000529

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000757

Gnomad ASJ exome

AF:

0.000462

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000142

Gnomad OTH exome

AF:

0.000425

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1419302

Hom.:

Cov.:

AF XY:

0.0000285

AC XY:

AN XY:

702300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32534

American (AMR)

AF:

0.000132

AC:

AN:

37750

Ashkenazi Jewish (ASJ)

AF:

0.000707

AC:

AN:

25458

East Asian (EAS)

AF:

0.00

AC:

AN:

37532

South Asian (SAS)

AF:

0.00

AC:

AN:

81512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49042

Middle Eastern (MID)

AF:

0.000526

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000367

AC:

AN:

1090918

Other (OTH)

AF:

0.0000850

AC:

AN:

58850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.000196

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.000956

AC:

AN:

2092

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

Alfa

AF:

0.0000863

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000342

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.972C>G (p.S324R) alteration is located in exon 7 (coding exon 7) of the OGFR gene. This alteration results from a C to G substitution at nucleotide position 972, causing the serine (S) at amino acid position 324 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0091

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PhyloP100

-0.97

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.026

Sift

Benign

0.087

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.85

P;.

Vest4

0.047

MutPred

0.30

Loss of glycosylation at S324 (P = 0.0077);.;

MVP

0.28

MPC

0.81

ClinPred

0.037

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.081

Mutation Taster

=97/3

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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chr20-62812587-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over