rs1975285

chr8-56446123-G-Cchr8-56446123-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135690.3(PENK):c.-3-167C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 732,162 control chromosomes in the GnomAD database, including 232,902 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 0.83 (52190 hom., cov: 33)
  • Exomes 𝑓: 0.79 (180712 hom.)
• Consequence: PENK NM_001135690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PENK	NM_001135690.3	c.-3-167C>G		intron_variant		ENST00000451791.7
PENK-AS1	NR_125813.1	n.317G>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PENK	ENST00000451791.7	c.-3-167C>G		intron_variant		1	NM_001135690.3	P1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125427 AN: 152048 Hom.: 52134 Cov.: 33

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.788 AC: 456906 AN: 579996 Hom.: 180712 Cov.: 8 AF XY: 0.789 AC XY: 233614 AN XY: 296048

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.849

Gnomad4 ASJ exome AF: 0.804

Gnomad4 EAS exome AF: 0.870

Gnomad4 SAS exome AF: 0.847

Gnomad4 FIN exome AF: 0.804

Gnomad4 NFE exome AF: 0.764

Gnomad4 OTH exome AF: 0.794

GnomAD4 genome AF: 0.825 AC: 125545 AN: 152166 Hom.: 52190 Cov.: 33 AF XY: 0.825 AC XY: 61389 AN XY: 74378

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.820

Alfa AF: 0.801 Hom.: 6107

Bravo AF: 0.831

Asia WGS AF: 0.883 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.9
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1975285; hg19: chr8-57358682;