8-56440625-A-ATGTG

Variant names:

• chr8-56440625-A-ATGTG
• rs3138832
• ENST00000517415.1:c.130-3553_130-3550dupCACA

Variant summary

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

The ENST00000517415.1(PENK):​c.130-3553_130-3550dupCACA 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 0.049 (476 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 (AFR) allele frequency at 95% confidence interval = 0.146 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.130-3553_130-3550dupCACA		intron_variant	Intron 1 of 1	3		ENSP00000430268.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7307 AN: 148976 Hom.: 476 Cov.: 0

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00392

Gnomad SAS AF: 0.00550

Gnomad FIN AF: 0.000302

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0492 AC: 7328 AN: 149064 Hom.: 476 Cov.: 0 AF XY: 0.0480 AC XY: 3483 AN XY: 72576

African (AFR) AF: 0.149 AC: 6064 AN: 40752

American (AMR) AF: 0.0638 AC: 952 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.000292 AC: 1 AN: 3426

East Asian (EAS) AF: 0.00413 AC: 21 AN: 5082

South Asian (SAS) AF: 0.00488 AC: 23 AN: 4714

European-Finnish (FIN) AF: 0.000302 AC: 3 AN: 9930

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00266 AC: 178 AN: 66994

Other (OTH) AF: 0.0413 AC: 85 AN: 2060

Alfa AF: 0.000542 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;