dbSNP rs2576573: PENK:c.138+400C>T (chr8-56445416-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135690.3(PENK):c.138+400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 443,382 control chromosomes in the GnomAD database, including 41,561 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 0.39 ( 12078 hom., cov: 32)

Exomes 𝑓: 0.44 ( 29483 hom. )

Consequence

PENK
NM_001135690.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.515

Publications

8 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PENK	NM_001135690.3 link	c.138+400C>T		intron_variant	Intron 3 of 3	ENST00000451791.7	NP_001129162.1	P01210A0A024R7V4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PENK	ENST00000451791.7 link	c.138+400C>T		intron_variant	Intron 3 of 3	1	NM_001135690.3	ENSP00000400894.2		P01210

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58579

AN:

151912

Hom.:

12070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.392

GnomAD4 exome

AF:

0.444

AC:

129274

AN:

291352

Hom.:

29483

Cov.:

AF XY:

0.446

AC XY:

66362

AN XY:

148778

show subpopulations

African (AFR)

AF:

0.255

AC:

2381

AN:

9328

American (AMR)

AF:

0.378

AC:

4395

AN:

11618

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

5118

AN:

10228

East Asian (EAS)

AF:

0.353

AC:

9041

AN:

25638

South Asian (SAS)

AF:

0.502

AC:

4742

AN:

9440

European-Finnish (FIN)

AF:

0.522

AC:

11641

AN:

22304

Middle Eastern (MID)

AF:

0.510

AC:

746

AN:

1464

European-Non Finnish (NFE)

AF:

0.455

AC:

83086

AN:

182720

Other (OTH)

AF:

0.436

AC:

8124

AN:

18612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

3424

6848

10271

13695

17119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58608

AN:

152030

Hom.:

12078

Cov.:

AF XY:

0.388

AC XY:

28866

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.241

AC:

10018

AN:

41488

American (AMR)

AF:

0.356

AC:

5444

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1705

AN:

3468

East Asian (EAS)

AF:

0.353

AC:

1820

AN:

5162

South Asian (SAS)

AF:

0.472

AC:

2263

AN:

4796

European-Finnish (FIN)

AF:

0.535

AC:

5656

AN:

10568

Middle Eastern (MID)

AF:

0.490

AC:

142

AN:

290

European-Non Finnish (NFE)

AF:

0.447

AC:

30365

AN:

67956

Other (OTH)

AF:

0.391

AC:

826

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1784

3568

5352

7136

8920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.422

Hom.:

3378

Bravo

AF:

0.366

Asia WGS

AF:

0.413

AC:

1439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

(source)

DANN

Benign

0.69

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over