Genetic Variant NM_001135690.3:c.-3-167C>G (chr8-56446123-G-C) – 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.-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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.223

Publications

6 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:

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

PENK-AS1 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=-0.82).

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 rank	MANE	Protein	UniProt
PENK	NM_001135690.3 link	c.-3-167C>G		intron_variant	Intron 2 of 3	ENST00000451791.7	NP_001129162.1	P01210A0A024R7V4
PENK-AS1	NR_125813.1 link	n.317G>C		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PENK	ENST00000451791.7 link	c.-3-167C>G		intron_variant	Intron 2 of 3	1	NM_001135690.3	ENSP00000400894.2		P01210

Frequencies

GnomAD3 genomes

AF:

0.825

AC:

125427

AN:

152048

Hom.:

52134

Cov.:

show subpopulations

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.:

AF XY:

0.789

AC XY:

233614

AN XY:

296048

show subpopulations

African (AFR)

AF:

0.931

AC:

13270

AN:

14248

American (AMR)

AF:

0.849

AC:

15552

AN:

18328

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

11288

AN:

14036

East Asian (EAS)

AF:

0.870

AC:

26953

AN:

30968

South Asian (SAS)

AF:

0.847

AC:

36938

AN:

43636

European-Finnish (FIN)

AF:

0.804

AC:

30155

AN:

37516

Middle Eastern (MID)

AF:

0.793

AC:

1725

AN:

2176

European-Non Finnish (NFE)

AF:

0.764

AC:

297367

AN:

389298

Other (OTH)

AF:

0.794

AC:

23658

AN:

29790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4871

9742

14613

19484

24355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4180

8360

12540

16720

20900

<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:

0.825

AC:

125545

AN:

152166

Hom.:

52190

Cov.:

AF XY:

0.825

AC XY:

61389

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.928

AC:

38562

AN:

41564

American (AMR)

AF:

0.826

AC:

12643

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.797

AC:

2767

AN:

3472

East Asian (EAS)

AF:

0.870

AC:

4460

AN:

5128

South Asian (SAS)

AF:

0.849

AC:

4097

AN:

4828

European-Finnish (FIN)

AF:

0.801

AC:

8479

AN:

10582

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.763

AC:

51831

AN:

67972

Other (OTH)

AF:

0.820

AC:

1734

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1132

2263

3395

4526

5658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.801

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

(source)

DANN

Benign

0.38

PhyloP100

-0.22

PromoterAI

-0.048

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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