chr8-53234771-T-C

Variant names:

• chr8-53234771-T-C
• rs77476023
• NM_000912.5:c.598A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000912.5(OPRK1):​c.598A>G​(p.Lys200Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,609,364 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: OPRK1 NM_000912.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29
• Publications: 1 publications found

Genes affected

OPRK1 (HGNC:8154): (opioid receptor kappa 1) This gene encodes an opioid receptor, which is a member of the 7 transmembrane-spanning G protein-coupled receptor family. It functions as a receptor for endogenous ligands, as well as a receptor for various synthetic opioids. Ligand binding results in inhibition of adenylate cyclase activity and neurotransmitter release. This opioid receptor plays a role in the perception of pain and mediating the hypolocomotor, analgesic and aversive actions of synthetic opioids. Variations in this gene have also been associated with alcohol dependence and opiate addiction. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

ENSG00000254687 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008436441).
• BP6: Variant 8-53234771-T-C is Benign according to our data. Variant chr8-53234771-T-C is described in ClinVar as Benign. ClinVar VariationId is 724740.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000912.5. 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
	OPRK1	NM_000912.5	MANE Select	c.598A>G	p.Lys200Glu	missense	Exon 3 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.598A>G	p.Lys200Glu	missense	Exon 3 of 4	NP_001305426.1	A0A5F9ZI09
	OPRK1	NM_001282904.2		c.331A>G	p.Lys111Glu	missense	Exon 4 of 5	NP_001269833.1	P41145-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.598A>G	p.Lys200Glu	missense	Exon 3 of 4	ENSP00000265572.3	P41145-1
	OPRK1	ENST00000520287.5	TSL:1	c.598A>G	p.Lys200Glu	missense	Exon 2 of 3	ENSP00000429706.1	P41145-1
	OPRK1	ENST00000524278.5	TSL:1	c.331A>G	p.Lys111Glu	missense	Exon 2 of 3	ENSP00000430923.1	P41145-2

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152204 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.00143

GnomAD2 exomes AF: 0.000423 AC: 106 AN: 250784 AF XY: 0.000354

Gnomad AFR exome AF: 0.00628

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000152 AC: 222 AN: 1457042 Hom.: 0 Cov.: 31 AF XY: 0.000140 AC XY: 101 AN XY: 723682

African (AFR) AF: 0.00590 AC: 197 AN: 33410

American (AMR) AF: 0.000202 AC: 9 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107886

Other (OTH) AF: 0.000249 AC: 15 AN: 60172

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152322 Hom.: 1 Cov.: 33 AF XY: 0.00149 AC XY: 111 AN XY: 74502

African (AFR) AF: 0.00568 AC: 236 AN: 41576

American (AMR) AF: 0.000392 AC: 6 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000656 Hom.: 1

Bravo AF: 0.00189

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000445 AC: 54

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.35	N
PhyloP100		2.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.083
Sift	Benign	0.24	T
Sift4G	Benign	0.92	T
Polyphen		0.078	B
Vest4		0.48
MVP		0.57
MPC		0.50
ClinPred		0.029	T
GERP RS		5.7
Varity_R		0.55
gMVP		0.74
Mutation Taster		=54/46	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: rs77476023; hg19: chr8-54147331;