Variant 6-71289093-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000370435.5(OGFRL1):c.157C>A(p.Pro53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,122,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

OGFRL1
ENST00000370435.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.793

Variant links:

Genes affected

OGFRL1 (HGNC:21378): (opioid growth factor receptor like 1) Predicted to enable opioid growth factor receptor activity. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

OGFRL1 links:

LINC00472 (HGNC:21380): (long intergenic non-protein coding RNA 472)

LINC00472 links:

LOC124901339 (HGNC:):

LOC124901339 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051879764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGFRL1	NM_024576.5 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	1/7	ENST00000370435.5	NP_078852.3
LOC124901339	XR_007059640.1 linkuse as main transcript	n.5782-4153G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGFRL1	ENST00000370435.5 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	1/7	1	NM_024576.5	ENSP00000359464	P1
LINC00472	ENST00000710850.1 linkuse as main transcript	n.355-55436G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000539

AC:

AN:

148476

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000120

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000143

AC:

139

AN:

974102

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

460612

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000162

Gnomad4 OTH exome

AF:

0.0000282

GnomAD4 genome

AF:

0.0000539

AC:

AN:

148476

Hom.:

Cov.:

AF XY:

0.0000553

AC XY:

AN XY:

72340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000120

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 31, 2023

The c.157C>A (p.P53T) alteration is located in exon 1 (coding exon 1) of the OGFRL1 gene. This alteration results from a C to A substitution at nucleotide position 157, causing the proline (P) at amino acid position 53 to be replaced by a threonine (T). 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

0.065

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.94

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.26

REVEL

Benign

0.032

Sift

Benign

0.37

Sift4G

Benign

0.50

Polyphen

0.0070

Vest4

0.063

MutPred

0.23

Loss of catalytic residue at P53 (P = 0.0064);

MVP

0.13

MPC

1.4

ClinPred

0.083

GERP RS

1.1

Varity_R

0.031

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over