8-56440625-ATGTGTGTGTGTG-ATGTGTGTGTGTGTG

Variant names:

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

Variant summary

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

The ENST00000517415.1(PENK):​c.130-3551_130-3550dupCA 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 0.41 (12610 hom., cov: 0)
• Consequence: PENK ENST00000517415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• 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 (EAS) allele frequency at 95% confidence interval = 0.535 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_130-3550dupCA		intron_variant	Intron 1 of 1	3		ENSP00000430268.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 60511 AN: 148844 Hom.: 12613 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.406 AC: 60514 AN: 148930 Hom.: 12610 Cov.: 0 AF XY: 0.410 AC XY: 29693 AN XY: 72506

African (AFR) AF: 0.268 AC: 10916 AN: 40714

American (AMR) AF: 0.364 AC: 5422 AN: 14898

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1693 AN: 3422

East Asian (EAS) AF: 0.552 AC: 2803 AN: 5076

South Asian (SAS) AF: 0.486 AC: 2287 AN: 4704

European-Finnish (FIN) AF: 0.541 AC: 5363 AN: 9914

Middle Eastern (MID) AF: 0.510 AC: 148 AN: 290

European-Non Finnish (NFE) AF: 0.458 AC: 30670 AN: 66958

Other (OTH) AF: 0.415 AC: 855 AN: 2060

Alfa AF: 0.290 Hom.: 512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

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;