6-71289018-G-A

Variant names:

• chr6-71289018-G-A
• rs754346241
• NM_024576.5:c.82G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024576.5(OGFRL1):​c.82G>A​(p.Glu28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000827 in 1,209,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 1 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: 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=0.29933035).

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.82G>A	p.Glu28Lys	missense	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.82G>A	p.Glu28Lys	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.82G>A	p.Glu28Lys	missense	Exon 1 of 7	ENSP00000359464.3	Q5TC84
	LINC00472	ENST00000412751.5	TSL:3	n.106-11704C>T		intron	N/A
	LINC00472	ENST00000423255.5	TSL:3	n.46-4078C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000686 AC: 1 AN: 145868 AF XY: 0.0000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.27e-7 AC: 1 AN: 1209126 Hom.: 0 Cov.: 29 AF XY: 0.00000167 AC XY: 1 AN XY: 599842

African (AFR) AF: 0.00 AC: 0 AN: 24386

American (AMR) AF: 0.00 AC: 0 AN: 30178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18214

East Asian (EAS) AF: 0.00 AC: 0 AN: 22548

South Asian (SAS) AF: 0.00 AC: 0 AN: 65614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4274

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 971048

Other (OTH) AF: 0.00 AC: 0 AN: 45220

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000886 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.082
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.074	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.84	P
Vest4		0.15
MutPred		0.14		Gain of methylation at E28 (P = 0.0085)
MVP		0.35
MPC		2.6
ClinPred		0.72	D
GERP RS		2.0
PromoterAI		-0.065	Neutral
Varity_R		0.13
gMVP		0.41
Mutation Taster		=55/45	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

Other links and lift over

dbSNP: rs754346241; hg19: chr6-71998721;