OGFRL1 p.Asp68Glu

Variant names:

• chr6-71289140-C-A
• NM_024576.5:c.204C>A
• OGFRL1 p.Asp68Glu

Your query was ambiguous. Multiple possible variants found:

• chr6-71289140-C-A
• chr6-71289140-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024576.5(OGFRL1):​c.204C>A​(p.Asp68Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 0 publications found

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]

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

LOC124901339 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031741112).

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.204C>A	p.Asp68Glu	missense	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.204C>A	p.Asp68Glu	missense	Exon 1 of 7	NP_001311195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFRL1	ENST00000370435.5	TSL:1 MANE Select	c.204C>A	p.Asp68Glu	missense	Exon 1 of 7	ENSP00000359464.3	Q5TC84
	LINC00472	ENST00000412751.5	TSL:3	n.106-11826G>T		intron	N/A
	LINC00472	ENST00000423255.5	TSL:3	n.46-4200G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 945062 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 445040

African (AFR) AF: 0.00 AC: 0 AN: 18142

American (AMR) AF: 0.00 AC: 0 AN: 4194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8556

East Asian (EAS) AF: 0.00 AC: 0 AN: 11868

South Asian (SAS) AF: 0.00 AC: 0 AN: 18516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835682

Other (OTH) AF: 0.00 AC: 0 AN: 33908

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.39	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.033
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.040
Sift	Benign	0.83	T
Sift4G	Benign	1.0	T
PromoterAI		0.34	Neutral
Varity_R		0.036
gMVP		0.082
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-71998843;