Menu
GeneBe

8-56441293-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001135690.3(PENK):c.783C>T(p.Tyr261=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,605,600 control chromosomes in the GnomAD database, including 440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 231 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 209 hom. )

Consequence

PENK
NM_001135690.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0430
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-56441293-G-A is Benign according to our data. Variant chr8-56441293-G-A is described in ClinVar as [Benign]. Clinvar id is 780755.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.043 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PENKNM_001135690.3 linkuse as main transcriptc.783C>T p.Tyr261= synonymous_variant 4/4 ENST00000451791.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PENKENST00000451791.7 linkuse as main transcriptc.783C>T p.Tyr261= synonymous_variant 4/41 NM_001135690.3 P1
PENKENST00000314922.3 linkuse as main transcriptc.783C>T p.Tyr261= synonymous_variant 2/21 P1
PENKENST00000517415.1 linkuse as main transcriptc.130-4217C>T intron_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0297
AC:
4516
AN:
152142
Hom.:
229
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0114
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0221
GnomAD3 exomes
AF:
0.00780
AC:
1914
AN:
245534
Hom.:
87
AF XY:
0.00570
AC XY:
760
AN XY:
133258
show subpopulations
Gnomad AFR exome
AF:
0.106
Gnomad AMR exome
AF:
0.00510
Gnomad ASJ exome
AF:
0.000314
Gnomad EAS exome
AF:
0.000278
Gnomad SAS exome
AF:
0.000232
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000143
Gnomad OTH exome
AF:
0.00323
GnomAD4 exome
AF:
0.00313
AC:
4555
AN:
1453340
Hom.:
209
Cov.:
32
AF XY:
0.00268
AC XY:
1937
AN XY:
722844
show subpopulations
Gnomad4 AFR exome
AF:
0.112
Gnomad4 AMR exome
AF:
0.00564
Gnomad4 ASJ exome
AF:
0.000429
Gnomad4 EAS exome
AF:
0.000177
Gnomad4 SAS exome
AF:
0.000303
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000123
Gnomad4 OTH exome
AF:
0.00698
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0298
AC:
4532
AN:
152260
Hom.:
231
Cov.:
32
AF XY:
0.0293
AC XY:
2180
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.103
Gnomad4 AMR
AF:
0.0113
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0218
Alfa
AF:
0.0161
Hom.:
33
Bravo
AF:
0.0347
Asia WGS
AF:
0.00577
AC:
20
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
0.69
Dann
Benign
0.82

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.

Other links and lift over

dbSNP: rs34189005; hg19: chr8-57353852; COSMIC: COSV59240020; COSMIC: COSV59240020; API