chr6-71289016-C-T

Variant names:

• chr6-71289016-C-T
• rs867388532
• NM_024576.5:c.80C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024576.5(OGFRL1):​c.80C>T​(p.Ser27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000044 in 1,364,970 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: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1035524).

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>T	p.Ser27Leu	missense	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.80C>T	p.Ser27Leu	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.80C>T	p.Ser27Leu	missense	Exon 1 of 7	ENSP00000359464.3	Q5TC84
	LINC00472	ENST00000412751.5	TSL:3	n.106-11702G>A		intron	N/A
	LINC00472	ENST00000423255.5	TSL:3	n.46-4076G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147232 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

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

GnomAD2 exomes AF: 0.00000665 AC: 1 AN: 150408 AF XY: 0.0000116

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: 0.0000143

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000328 AC: 4 AN: 1217738 Hom.: 0 Cov.: 29 AF XY: 0.00000165 AC XY: 1 AN XY: 604548

African (AFR) AF: 0.00 AC: 0 AN: 24516

American (AMR) AF: 0.0000982 AC: 3 AN: 30552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18462

East Asian (EAS) AF: 0.00 AC: 0 AN: 22866

South Asian (SAS) AF: 0.00 AC: 0 AN: 67240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4392

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 975818

Other (OTH) AF: 0.00 AC: 0 AN: 45666

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147232 Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 1 AN XY: 71678

African (AFR) AF: 0.00 AC: 0 AN: 40742

American (AMR) AF: 0.000134 AC: 2 AN: 14874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66122

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.79
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.077
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0090	B
Vest4		0.14
MutPred		0.13		Loss of phosphorylation at S27 (P = 0.0103)
MVP		0.27
MPC		1.1
ClinPred		0.70	D
GERP RS		1.1
PromoterAI		-0.013	Neutral
Varity_R		0.12
gMVP		0.30
Mutation Taster		=81/19	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: rs867388532; hg19: chr6-71998719;