20-62812432-T-G

Variant names:

• chr20-62812432-T-G
• rs1651216281
• NM_007346.4:c.817T>G
• OGFR p.Phe273Val

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007346.4(OGFR):​c.817T>G​(p.Phe273Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. F273L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OGFR NM_007346.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007346.4. 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
	OGFR	NM_007346.4	MANE Select	c.817T>G	p.Phe273Val	missense	Exon 7 of 7	NP_031372.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFR	ENST00000290291.10	TSL:1 MANE Select	c.817T>G	p.Phe273Val	missense	Exon 7 of 7	ENSP00000290291.6	Q9NZT2-1
	OGFR	ENST00000892718.1		c.988T>G	p.Phe330Val	missense	Exon 8 of 8	ENSP00000562777.1
	OGFR	ENST00000892717.1		c.817T>G	p.Phe273Val	missense	Exon 9 of 9	ENSP00000562776.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432888 Hom.: 0 Cov.: 64 AF XY: 0.00 AC XY: 0 AN XY: 710142

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32776

American (AMR) AF: 0.0000244 AC: 1 AN: 40972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 38328

South Asian (SAS) AF: 0.00 AC: 0 AN: 82868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098086

Other (OTH) AF: 0.00 AC: 0 AN: 59068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0060	D
Varity_R		0.43
gMVP		0.69
Mutation Taster		=65/35	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1651216281;

hg19: chr20-61443784;