Variant chr6-71293327-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024576.5(OGFRL1):c.269A>C(p.Lys90Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 1 hom. )

Consequence

OGFRL1
NM_024576.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.59

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41843906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGFRL1	NM_024576.5 linkuse as main transcript	c.269A>C	p.Lys90Thr	missense_variant	2/7	ENST00000370435.5
LOC124901339	XR_007059640.1 linkuse as main transcript	n.5782-8387T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGFRL1	ENST00000370435.5 linkuse as main transcript	c.269A>C	p.Lys90Thr	missense_variant	2/7	1	NM_024576.5	P1
LINC00472	ENST00000710850.1 linkuse as main transcript	n.355-59670T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000576

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:

0.000478

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251344

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461604

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Oct 17, 2023

The c.269A>C (p.K90T) alteration is located in exon 2 (coding exon 2) of the OGFRL1 gene. This alteration results from a A to C substitution at nucleotide position 269, causing the lysine (K) at amino acid position 90 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.036

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Benign

0.090

Sift4G

Uncertain

0.036

Polyphen

1.0

Vest4

0.64

MutPred

0.30

Loss of methylation at K90 (P = 0.0025);

MVP

0.70

MPC

1.1

ClinPred

0.15

GERP RS

5.8

Varity_R

0.23

gMVP

0.51

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