20-62812307-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGFR	NM_007346.4	c.692C>T	p.Pro231Leu	missense_variant	Exon 7 of 7	ENST00000290291.10	NP_031372.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGFR	ENST00000290291.10	c.692C>T	p.Pro231Leu	missense_variant	Exon 7 of 7	1	NM_007346.4	ENSP00000290291.6
OGFR	ENST00000370461.5	c.536C>T	p.Pro179Leu	missense_variant	Exon 5 of 5	2		ENSP00000359491.1

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

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000370

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.692C>T (p.P231L) alteration is located in exon 7 (coding exon 7) of the OGFR gene. This alteration results from a C to T substitution at nucleotide position 692, causing the proline (P) at amino acid position 231 to be replaced by a leucine (L). 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	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;T;.
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-8.6	D;.;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D;.;D
Sift4G	Benign	0.073	T;D;D
Polyphen		1.0	D;.;.
Vest4		0.68
MutPred		0.74		Gain of loop (P = 0.024);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

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

LitVar

Other links and lift over

dbSNP: rs1281729415; hg19: chr20-61443659;