Genetic Variant PNOC:c.*47+739G>C (chr8-28340230-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_006228.5(PNOC):c.*47+739G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,156 control chromosomes in the GnomAD database, including 43,011 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 0.73 ( 42977 hom., cov: 32)

Exomes 𝑓: 0.88 ( 34 hom. )

Consequence

PNOC
NM_006228.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

4 publications found

Variant links:

Genes affected

PNOC (HGNC:9163): (prepronociceptin) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include nociceptin, nocistatin, and orphanin FQ2 (OFQ2). Nociceptin, also known as orphanin FQ, is a 17-amino acid neuropeptide that binds to the nociceptin receptor to induce increased pain sensitivity, and may additionally regulate body temperature, learning and memory, and hunger. Another product of the encoded preproprotein, nocistatin, may inhibit the effects of nociceptin. [provided by RefSeq, Jul 2015]

PNOC links:

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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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PNOC	NM_006228.5 link	c.*47+739G>C	intron_variant	Intron 3 of 3	ENST00000301908.8	NP_006219.1	Q13519-1
PNOC	NM_001284244.2 link	c.*47+739G>C	intron_variant	Intron 2 of 2		NP_001271173.1	Q13519-2
PNOC	XM_005273532.3 link	c.520+797G>C	intron_variant	Intron 3 of 3		XP_005273589.1
PNOC	XM_011544559.3 link	c.520+797G>C	intron_variant	Intron 3 of 3		XP_011542861.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PNOC	ENST00000301908.8 link	c.*47+739G>C	intron_variant	Intron 3 of 3	1	NM_006228.5	ENSP00000301908.3	Q13519-1
PNOC	ENST00000522209.1 link	c.*47+739G>C	intron_variant	Intron 2 of 2	2		ENSP00000430145.1	Q13519-2
PNOC	ENST00000519592.5 link	n.*22G>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111457

AN:

151948

Hom.:

42973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.952

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.822

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.689

Gnomad FIN

AF:

0.827

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.777

GnomAD4 exome

AF:

0.878

AC:

AN:

Hom.:

Cov.:

AF XY:

0.871

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.914

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.733

AC:

111497

AN:

152066

Hom.:

42977

Cov.:

AF XY:

0.731

AC XY:

54318

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.483

AC:

20002

AN:

41408

American (AMR)

AF:

0.780

AC:

11927

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.822

AC:

2851

AN:

3470

East Asian (EAS)

AF:

0.580

AC:

2997

AN:

5164

South Asian (SAS)

AF:

0.689

AC:

3320

AN:

4820

European-Finnish (FIN)

AF:

0.827

AC:

8763

AN:

10594

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58868

AN:

67998

Other (OTH)

AF:

0.779

AC:

1647

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1318

2637

3955

5274

6592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.739

Hom.:

2526

Bravo

AF:

0.720

Asia WGS

AF:

0.655

AC:

2277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.034

(source)

DANN

Benign

0.45

PhyloP100

-1.7

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