rs6474063

Positions:

• chr8-56442986-C-T

Variant summary

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

The NM_001135690.3(PENK):​c.139-1049G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,032 control chromosomes in the GnomAD database, including 52,162 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 0.83 (52162 hom., cov: 32)
• Consequence: PENK NM_001135690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

Genes affected

PENK (HGNC:8831): (proenkephalin) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the pentapeptide opioids Met-enkephalin and Leu-enkephalin, which are stored in synaptic vesicles, then released into the synapse where they bind to mu- and delta-opioid receptors to modulate the perception of pain. Other non-opioid cleavage products may function in distinct biological activities. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PENK	NM_001135690.3	c.139-1049G>A		intron_variant		ENST00000451791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PENK	ENST00000451791.7	c.139-1049G>A		intron_variant		1	NM_001135690.3	P1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125349 AN: 151918 Hom.: 52108 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.825 AC: 125463 AN: 152032 Hom.: 52162 Cov.: 32 AF XY: 0.826 AC XY: 61368 AN XY: 74332

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.820

Alfa AF: 0.804 Hom.: 8334

Bravo AF: 0.832

Asia WGS AF: 0.882 AC: 3025 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.21

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: rs6474063; hg19: chr8-57355545;