chr6-71301699-C-T

Variant names:

• chr6-71301699-C-T
• rs1766396240
• NM_024576.5:c.1006C>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.1006C>T​(p.His336Tyr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• 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=0.09481308).

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.1006C>T	p.His336Tyr	missense	Exon 7 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.1009C>T	p.His337Tyr	missense	Exon 7 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.1006C>T	p.His336Tyr	missense	Exon 7 of 7	ENSP00000359464.3	Q5TC84
	OGFRL1	ENST00000650315.1		c.409C>T	p.His137Tyr	missense	Exon 7 of 7	ENSP00000496790.1	A0A3B3IRI0
	LINC00472	ENST00000412751.5	TSL:3	n.105+8597G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.74
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.081
Sift	Benign	0.081	T
Sift4G	Uncertain	0.041	D
Polyphen		0.75	P
Vest4		0.17
MutPred		0.16		Gain of phosphorylation at H336 (P = 0.0168)
MVP		0.14
MPC		0.63
ClinPred		0.17	T
GERP RS		5.2
Varity_R		0.039
gMVP		0.26
Mutation Taster		=87/13	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: rs1766396240; hg19: chr6-72011402;