Variant 8-56441429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001135690.3(PENK):c.647G>A(p.Arg216Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,614,024 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

PENK
NM_001135690.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.23

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03092894).

BP6

Variant 8-56441429-C-T is Benign according to our data. Variant chr8-56441429-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 714380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PENK	NM_001135690.3 linkuse as main transcript	c.647G>A	p.Arg216Lys	missense_variant	4/4	ENST00000451791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PENK	ENST00000451791.7 linkuse as main transcript	c.647G>A	p.Arg216Lys	missense_variant	4/4	1	NM_001135690.3	P1
PENK	ENST00000314922.3 linkuse as main transcript	c.647G>A	p.Arg216Lys	missense_variant	2/2	1		P1
PENK	ENST00000517415.1 linkuse as main transcript	c.130-4353G>A		intron_variant		3
PENK	ENST00000523274.1 linkuse as main transcript	n.569G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00473

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000314

AC:

AN:

251330

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

201

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00139

AC:

212

AN:

152334

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00474

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000783

Hom.:

Bravo

AF:

0.00158

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

D;D

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.9

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.83

MVP

0.60

MPC

0.26

ClinPred

0.10

GERP RS

5.9

Varity_R

0.72

gMVP

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over