rs2609998

Variant names:

• chr8-56447475-G-A
• rs2609998
• ENST00000961479.1:c.-248C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000961479.1(PENK):​c.-248C>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 0.385 in 151,368 control chromosomes in the GnomAD database, including 12,037 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 0.39 (12037 hom., cov: 29)
• Consequence: PENK ENST00000961479.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 8 publications found

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]

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000961479.1. 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
	PENK-AS1	NR_125813.1		n.694+975G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PENK	ENST00000961479.1		c.-248C>T		5_prime_UTR	Exon 1 of 4	ENSP00000631538.1
	PENK	ENST00000961478.1		c.-60+409C>T		intron	N/A	ENSP00000631537.1
	PENK-AS1	ENST00000518662.5	TSL:2	n.694+975G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58318 AN: 151250 Hom.: 12029 Cov.: 29

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.385 AC: 58347 AN: 151368 Hom.: 12037 Cov.: 29 AF XY: 0.388 AC XY: 28659 AN XY: 73870

African (AFR) AF: 0.243 AC: 10026 AN: 41280

American (AMR) AF: 0.357 AC: 5432 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1762 AN: 5048

South Asian (SAS) AF: 0.469 AC: 2237 AN: 4766

European-Finnish (FIN) AF: 0.533 AC: 5575 AN: 10452

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30275 AN: 67816

Other (OTH) AF: 0.392 AC: 823 AN: 2102

Alfa AF: 0.412 Hom.: 1544

Bravo AF: 0.366

Asia WGS AF: 0.413 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.6
DANN	Benign	0.85
PhyloP100		1.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2609998;

hg19: chr8-57360034;