8-56440625-ATGTGTGTGTGTG-ATGTGTGTGTG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.106 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

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0175

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0490

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;