6-71289129-C-G

Variant names:

• chr6-71289129-C-G
• rs1321280644
• NM_024576.5:c.193C>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.193C>G​(p.Pro65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,108,090 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.676
• 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: 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=0.048249125).

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>G	p.Pro65Ala	missense	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.193C>G	p.Pro65Ala	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>G	p.Pro65Ala	missense	Exon 1 of 7	ENSP00000359464.3	Q5TC84
	LINC00472	ENST00000412751.5	TSL:3	n.106-11815G>C		intron	N/A
	LINC00472	ENST00000423255.5	TSL:3	n.46-4189G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149310 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000666

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: 0.0000299

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000177 AC: 17 AN: 958676 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 5 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: 0.0000201 AC: 17 AN: 843886

Other (OTH) AF: 0.00 AC: 0 AN: 34776

GnomAD4 genome AF: 0.0000268 AC: 4 AN: 149414 Hom.: 0 Cov.: 31 AF XY: 0.0000549 AC XY: 4 AN XY: 72926

African (AFR) AF: 0.0000242 AC: 1 AN: 41244

American (AMR) AF: 0.0000665 AC: 1 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66958

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Benign	0.051
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.7
DANN	Benign	0.84
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.68
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.048
Sift	Benign	0.92	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.18		Gain of methylation at R60 (P = 0.1238)
MVP		0.076
MPC		1.2
ClinPred		0.041	T
GERP RS		0.34
PromoterAI		-0.00090	Neutral
Varity_R		0.029
gMVP		0.16
Mutation Taster		=94/6	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;