6-71301698-T-G

Variant names:

• chr6-71301698-T-G
• rs1582561147
• NM_024576.5:c.1005T>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.1005T>G​(p.Ser335Arg) 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: 0.152
• 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=0.05052063).

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.1005T>G	p.Ser335Arg	missense	Exon 7 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.1008T>G	p.Ser336Arg	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.1005T>G	p.Ser335Arg	missense	Exon 7 of 7	ENSP00000359464.3	Q5TC84
	OGFRL1	ENST00000650315.1		c.408T>G	p.Ser136Arg	missense	Exon 7 of 7	ENSP00000496790.1	A0A3B3IRI0
	LINC00472	ENST00000412751.5	TSL:3	n.105+8598A>C		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	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.77
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.15
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.021
Sift	Benign	0.31	T
Sift4G	Benign	0.53	T
Polyphen		0.45	P
Vest4		0.068
MutPred		0.22		Gain of MoRF binding (P = 0.018)
MVP		0.085
MPC		0.35
ClinPred		0.082	T
GERP RS		-0.53
Varity_R		0.030
gMVP		0.17
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1582561147; hg19: chr6-72011401;