NM_007346.4:c.482A>G

Variant names:

• chr20-62811478-A-G
• rs781355636
• NM_007346.4:c.482A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_007346.4(OGFR):​c.482A>G​(p.Gln161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,611,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000041 (1 hom.)
• Consequence: OGFR NM_007346.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.103
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045168012).
• BP6: Variant 20-62811478-A-G is Benign according to our data. Variant chr20-62811478-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3409876.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGFR	NM_007346.4	c.482A>G	p.Gln161Arg	missense_variant	Exon 6 of 7	ENST00000290291.10	NP_031372.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGFR	ENST00000290291.10	c.482A>G	p.Gln161Arg	missense_variant	Exon 6 of 7	1	NM_007346.4	ENSP00000290291.6
OGFR	ENST00000370461.5	c.326A>G	p.Gln109Arg	missense_variant	Exon 4 of 5	2		ENSP00000359491.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000408 AC: 10 AN: 245038 AF XY: 0.0000526

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.000405

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000411 AC: 60 AN: 1459344 Hom.: 1 Cov.: 30 AF XY: 0.0000372 AC XY: 27 AN XY: 725750

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000449 AC: 2 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 16 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52130

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111530

Other (OTH) AF: 0.0000829 AC: 5 AN: 60324

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000249 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 11, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0020
DANN	Benign	0.40
DEOGEN2	Benign	0.0048	T;T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.20	T;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.1	L;.;.
PhyloP100		-0.10
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.31	N;.;N
REVEL	Benign	0.024
Sift	Benign	0.26	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.15
MutPred		0.39		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);.;
MVP		0.27
MPC		0.30
ClinPred		0.041	T
GERP RS		-9.1
Varity_R		0.021
gMVP		0.23
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs781355636; hg19: chr20-61442830;