8-56440625-ATGTGTGTGTGTG-ATGTGTGTG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000517415.1(PENK):​c.130-3553_130-3550delCACA 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 0.0062 (8 hom., cov: 0)
• Consequence: PENK ENST00000517415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0062 (925/149080) while in subpopulation AFR AF = 0.0205 (834/40760). AF 95% confidence interval is 0.0193. There are 8 homozygotes in GnomAd4. There are 434 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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_130-3550delCACA		intron_variant	Intron 1 of 1	3		ENSP00000430268.1

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 922 AN: 148992 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00188

Gnomad ASJ AF: 0.00263

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00423

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000403

Gnomad OTH AF: 0.00294

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

GnomAD4 genome AF: 0.00620 AC: 925 AN: 149080 Hom.: 8 Cov.: 0 AF XY: 0.00598 AC XY: 434 AN XY: 72588

African (AFR) AF: 0.0205 AC: 834 AN: 40760

American (AMR) AF: 0.00188 AC: 28 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.00263 AC: 9 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00424 AC: 20 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9930

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

European-Non Finnish (NFE) AF: 0.000403 AC: 27 AN: 66992

Other (OTH) AF: 0.00291 AC: 6 AN: 2062

Alfa AF: 0.00 Hom.: 512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.54

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;