rs768464574

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001007125.3(LKAAEAR1):c.539C>T(p.Pro180Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,525,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LKAAEAR1
NM_001007125.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0510

Publications

0 publications found

Variant links:

Genes affected

LKAAEAR1 (HGNC:33718): (LKAAEAR motif containing 1)

LKAAEAR1 links:

OPRL1 (HGNC:8155): (opioid related nociceptin receptor 1) The protein encoded by this gene is a member of the 7 transmembrane-spanning G protein-coupled receptor family, and functions as a receptor for the endogenous, opioid-related neuropeptide, nociceptin/orphanin FQ. This receptor-ligand system modulates a variety of biological functions and neurobehavior, including stress responses and anxiety behavior, learning and memory, locomotor activity, and inflammatory and immune responses. A promoter region between this gene and the 5'-adjacent RGS19 (regulator of G-protein signaling 19) gene on the opposite strand functions bi-directionally as a core-promoter for both genes, suggesting co-operative transcriptional regulation of these two functionally related genes. Alternatively spliced transcript variants have been described 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]

OPRL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013404667).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007125.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPRL1	NM_182647.4	MANE Select	c.-185+3217G>A		intron	N/A	NP_872588.1	P41146-1
LKAAEAR1	NM_001353425.2	MANE Select	c.525+14C>T		intron	N/A	NP_001340354.1	Q8TD35-1
LKAAEAR1	NM_001007125.3		c.539C>T	p.Pro180Leu	missense	Exon 2 of 2	NP_001007126.1	Q8TD35-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LKAAEAR1	ENST00000308906.6	TSL:1	c.539C>T	p.Pro180Leu	missense	Exon 2 of 2	ENSP00000310801.2	Q8TD35-2
OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.-185+3217G>A		intron	N/A	ENSP00000336843.2	P41146-1
LKAAEAR1	ENST00000302096.5	TSL:2 MANE Select	c.525+14C>T		intron	N/A	ENSP00000302763.4	Q8TD35-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000121

AC:

AN:

124314

AF XY:

0.0000876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000730

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:

0.0000131

AC:

AN:

1373220

Hom.:

Cov.:

AF XY:

0.0000133

AC XY:

AN XY:

676304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30476

American (AMR)

AF:

0.000567

AC:

AN:

31740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23400

East Asian (EAS)

AF:

0.00

AC:

AN:

35174

South Asian (SAS)

AF:

0.00

AC:

AN:

77784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068218

Other (OTH)

AF:

0.00

AC:

AN:

56726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.000262

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000270

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.6

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.98

PhyloP100

-0.051

PROVEAN

Benign

3.3

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.75

Vest4

0.11

MutPred

0.14

Loss of loop (P = 0.0022)

MVP

0.22

MPC

0.77

ClinPred

0.081

GERP RS

2.2

gMVP

0.014

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over