Genetic Variant OGFRL1:p.Ser27Trp (chr6-71289016-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024576.5(OGFRL1):c.80C>G(p.Ser27Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 147,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. S27L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Consequence

OGFRL1
NM_024576.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3502467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024576.5. 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
	OGFRL1	NM_024576.5	MANE Select	c.80C>G	p.Ser27Trp	missense	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.80C>G	p.Ser27Trp	missense	Exon 1 of 7	NP_001311195.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OGFRL1	ENST00000370435.5	TSL:1 MANE Select	c.80C>G	p.Ser27Trp	missense	Exon 1 of 7	ENSP00000359464.3	Q5TC84
LINC00472	ENST00000412751.5	TSL:3	n.106-11702G>C		intron	N/A
LINC00472	ENST00000423255.5	TSL:3	n.46-4076G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000491

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000136

AC:

AN:

147232

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71678

show subpopulations

African (AFR)

AF:

0.0000491

AC:

AN:

40742

American (AMR)

AF:

0.00

AC:

AN:

14874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4990

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66122

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

0.060

Eigen_PC

Benign

-0.030

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

4.0

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.37

MutPred

0.17

Loss of phosphorylation at S27 (P = 0.0103)

MVP

0.43

MPC

2.6

ClinPred

0.93

GERP RS

1.1

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.25

gMVP

0.41

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over