8-56440625-ATGTGTGTGTGTG-ATGTGTGTGTG

Variant names:

• chr8-56440625-ATG-A
• rs3138832
• ENST00000517415.1:c.130-3551_130-3550delCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000517415.1(PENK):​c.130-3551_130-3550delCA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.052 (303 hom., cov: 0)
• Consequence: PENK ENST00000517415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PENK	ENST00000517415.1	c.130-3551_130-3550delCA		intron_variant	Intron 1 of 1	3		ENSP00000430268.1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7789 AN: 148738 Hom.: 305 Cov.: 0

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0175

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0495

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

GnomAD4 genome AF: 0.0523 AC: 7788 AN: 148826 Hom.: 303 Cov.: 0 AF XY: 0.0525 AC XY: 3806 AN XY: 72446

African (AFR) AF: 0.108 AC: 4405 AN: 40718

American (AMR) AF: 0.0415 AC: 617 AN: 14882

Ashkenazi Jewish (ASJ) AF: 0.0175 AC: 60 AN: 3426

East Asian (EAS) AF: 0.0660 AC: 335 AN: 5078

South Asian (SAS) AF: 0.0851 AC: 401 AN: 4714

European-Finnish (FIN) AF: 0.0129 AC: 127 AN: 9862

Middle Eastern (MID) AF: 0.108 AC: 31 AN: 288

European-Non Finnish (NFE) AF: 0.0248 AC: 1657 AN: 66904

Other (OTH) AF: 0.0490 AC: 101 AN: 2060

Alfa AF: 0.0119 Hom.: 512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs3138832; hg19: chr8-57353184;