chr8-56440625-A-ATGTG

Position:

• chr8-56440625-A-ATGTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000517415.1(PENK):​c.130-3550_130-3549insCACA 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

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 -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PENK	ENST00000517415.1	c.130-3550_130-3549insCACA		intron_variant		3		ENSP00000430268

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

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0638

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.00413

Gnomad4 SAS AF: 0.00488

Gnomad4 FIN AF: 0.000302

Gnomad4 NFE AF: 0.00266

Gnomad4 OTH AF: 0.0413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3138832; hg19: chr8-57353184;