chr8-56442986-C-T

Variant names:

• chr8-56442986-C-T
• rs6474063
• NM_001135690.3:c.139-1049G>A

Variant summary

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

The NM_001135690.3(PENK):​c.139-1049G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,032 control chromosomes in the GnomAD database, including 52,162 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 (52162 hom., cov: 32)
• Consequence: PENK NM_001135690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135690.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PENK	NM_001135690.3	MANE Select	c.139-1049G>A		intron	N/A	NP_001129162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PENK	ENST00000451791.7	TSL:1 MANE Select	c.139-1049G>A		intron	N/A	ENSP00000400894.2
	PENK	ENST00000314922.3	TSL:1	c.139-1049G>A		intron	N/A	ENSP00000324248.3
	PENK	ENST00000518974.5	TSL:2	c.139-1049G>A		intron	N/A	ENSP00000428012.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125349 AN: 151918 Hom.: 52108 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.825 AC: 125463 AN: 152032 Hom.: 52162 Cov.: 32 AF XY: 0.826 AC XY: 61368 AN XY: 74332

African (AFR) AF: 0.928 AC: 38553 AN: 41540

American (AMR) AF: 0.826 AC: 12626 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2766 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4506 AN: 5182

South Asian (SAS) AF: 0.849 AC: 4087 AN: 4814

European-Finnish (FIN) AF: 0.801 AC: 8442 AN: 10538

Middle Eastern (MID) AF: 0.812 AC: 229 AN: 282

European-Non Finnish (NFE) AF: 0.763 AC: 51789 AN: 67900

Other (OTH) AF: 0.820 AC: 1731 AN: 2112

Alfa AF: 0.804 Hom.: 8334

Bravo AF: 0.832

Asia WGS AF: 0.882 AC: 3025 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.21
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6474063; hg19: chr8-57355545;