rs6512305

Variant names:

• chr20-64084917-G-A
• rs6512305
• NM_182647.4:c.-185+4565G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386971.1. 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
	OPRL1	NM_182647.4	MANE Select	c.-185+4565G>A		intron	N/A	NP_872588.1	P41146-1
	LKAAEAR1	NM_001386971.1		c.-15C>T		5_prime_UTR	Exon 1 of 4	NP_001373900.1	Q8TD35-1
	OPRL1	NM_001318853.2		c.-185+4565G>A		intron	N/A	NP_001305782.1	A0A5F9ZI64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.-185+4565G>A		intron	N/A	ENSP00000336843.2	P41146-1
	OPRL1	ENST00000355631.8	TSL:1	c.-34+4565G>A		intron	N/A	ENSP00000347848.4	P41146-1
	OPRL1	ENST00000879250.1		c.-234G>A		5_prime_UTR	Exon 1 of 5	ENSP00000549309.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 9 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.386 AC: 17 AN: 44

Other (OTH) AF: 0.600 AC: 6 AN: 10

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

African (AFR) AF: 0.461 AC: 19084 AN: 41418

American (AMR) AF: 0.560 AC: 8565 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1681 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3035 AN: 5138

South Asian (SAS) AF: 0.408 AC: 1968 AN: 4822

European-Finnish (FIN) AF: 0.577 AC: 6093 AN: 10556

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32195 AN: 67886

Other (OTH) AF: 0.490 AC: 1033 AN: 2108

Alfa AF: 0.475 Hom.: 2191

Bravo AF: 0.486

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		-1.2
PromoterAI		-0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs6512305; hg19: chr20-62716270;