rs1281729415

Variant names:

• chr20-62812307-C-T
• rs1281729415
• NM_007346.4:c.692C>T

Variant summary

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

The NM_007346.4(OGFR):​c.692C>T​(p.Pro231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 1,401,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: OGFR NM_007346.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18
• 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.692C>T	p.Pro231Leu	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.692C>T	p.Pro231Leu	missense	Exon 7 of 7	ENSP00000290291.6	Q9NZT2-1
	OGFR	ENST00000892718.1		c.863C>T	p.Pro288Leu	missense	Exon 8 of 8	ENSP00000562777.1
	OGFR	ENST00000892717.1		c.692C>T	p.Pro231Leu	missense	Exon 9 of 9	ENSP00000562776.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000428 AC: 6 AN: 1401340 Hom.: 0 Cov.: 50 AF XY: 0.00000434 AC XY: 3 AN XY: 691884

African (AFR) AF: 0.0000315 AC: 1 AN: 31770

American (AMR) AF: 0.00 AC: 0 AN: 36132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25092

East Asian (EAS) AF: 0.00 AC: 0 AN: 36104

South Asian (SAS) AF: 0.00 AC: 0 AN: 79456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1080892

Other (OTH) AF: 0.0000172 AC: 1 AN: 58022

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.74		Gain of loop (P = 0.024)
MVP		0.60
MPC		0.99
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.77
Mutation Taster		=80/20	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: rs1281729415; hg19: chr20-61443659;