rs6512305

Positions:

• chr20-64084917-G-A
• chr20-64084917-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386971.1(LKAAEAR1):​c.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,956 control chromosomes in the GnomAD database, including 18,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (18357 hom., cov: 32)
  • Exomes 𝑓: 0.47 (8 hom.)
• Consequence: LKAAEAR1 NM_001386971.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRL1	NM_182647.4	c.-185+4565G>A		intron_variant		ENST00000336866.7	NP_872588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRL1	ENST00000336866.7	c.-185+4565G>A		intron_variant		5	NM_182647.4	ENSP00000336843.2
OPRL1	ENST00000355631.8	c.-34+4565G>A		intron_variant		1		ENSP00000347848.4
OPRL1	ENST00000672146.3	c.-185+4565G>A		intron_variant				ENSP00000500894.2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74262 AN: 151772 Hom.: 18357 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.471 AC: 32 AN: 68 Hom.: 8 AF XY: 0.477 AC XY: 21 AN XY: 44

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.489 AC: 74292 AN: 151888 Hom.: 18357 Cov.: 32 AF XY: 0.494 AC XY: 36709 AN XY: 74244

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.490

Alfa AF: 0.476 Hom.: 2111

Bravo AF: 0.486

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs6512305; hg19: chr20-62716270;