8-56440625-ATGTGTGTGTGTG-ATGTGTGTG

Position:

• chr8-56440625-ATGTGTGTGTGTG-ATGTGTGTG

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.56440626_56440629delTGTG		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PENK	ENST00000517415.1	c.130-3553_130-3550delCACA		intron_variant		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

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.00188

Gnomad4 ASJ AF: 0.00263

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00424

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000403

Gnomad4 OTH AF: 0.00291

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;