8-56447926-T-C

Variant names:

• chr8-56447926-T-C
• rs2609997
• ENST00000961478.1:c.-102A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000961478.1(PENK):​c.-102A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,120 control chromosomes in the GnomAD database, including 11,075 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (11075 hom., cov: 32)
• Consequence: PENK ENST00000961478.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 14 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]

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000961478.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PENK-AS1	NR_125813.1		n.694+1426T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PENK	ENST00000961478.1		c.-102A>G		5_prime_UTR	Exon 1 of 4	ENSP00000631537.1
	PENK-AS1	ENST00000518662.5	TSL:2	n.694+1426T>C		intron	N/A
	PENK-AS1	ENST00000662661.1		n.264+1426T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53137 AN: 152002 Hom.: 11072 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.349 AC: 53148 AN: 152120 Hom.: 11075 Cov.: 32 AF XY: 0.353 AC XY: 26228 AN XY: 74346

African (AFR) AF: 0.116 AC: 4838 AN: 41536

American (AMR) AF: 0.344 AC: 5267 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1817 AN: 5164

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4816

European-Finnish (FIN) AF: 0.535 AC: 5653 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30330 AN: 67956

Other (OTH) AF: 0.366 AC: 770 AN: 2106

Alfa AF: 0.405 Hom.: 18810

Bravo AF: 0.324

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.52
PhyloP100		0.18

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2609997;

hg19: chr8-57360485;