NM_024576.5:c.193C>A

Variant names:

• chr6-71289129-C-A
• rs1321280644
• NM_024576.5:c.193C>A

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.193C>A​(p.Pro65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 958,676 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P65A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• 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=0.059146285).

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.193C>A	p.Pro65Thr	missense	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.193C>A	p.Pro65Thr	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.193C>A	p.Pro65Thr	missense	Exon 1 of 7	ENSP00000359464.3	Q5TC84
	LINC00472	ENST00000412751.5	TSL:3	n.106-11815G>T		intron	N/A
	LINC00472	ENST00000423255.5	TSL:3	n.46-4189G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000209 AC: 2 AN: 958676 Hom.: 0 Cov.: 30 AF XY: 0.00000221 AC XY: 1 AN XY: 451662

African (AFR) AF: 0.00 AC: 0 AN: 18498

American (AMR) AF: 0.00 AC: 0 AN: 4552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9048

East Asian (EAS) AF: 0.00 AC: 0 AN: 13624

South Asian (SAS) AF: 0.00 AC: 0 AN: 18598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2246

European-Non Finnish (NFE) AF: 0.00000118 AC: 1 AN: 843886

Other (OTH) AF: 0.0000288 AC: 1 AN: 34776

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.68
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.046
Sift	Benign	0.35	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.28		Gain of phosphorylation at P65 (P = 0.0015)
MVP		0.081
MPC		1.4
ClinPred		0.13	T
GERP RS		0.34
PromoterAI		-0.042	Neutral
Varity_R		0.042
gMVP		0.19
Mutation Taster		=92/8	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: rs1321280644; hg19: chr6-71998832;