dbSNP rs17058952: ENSG00000253690:n.230+22189T>C (chr8-28316837-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000521731.1(ENSG00000253690):n.230+22189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,112 control chromosomes in the GnomAD database, including 12,676 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 0.40 ( 12671 hom., cov: 32)

Exomes 𝑓: 0.35 ( 5 hom. )

Consequence

ENSG00000253690
ENST00000521731.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

Publications

4 publications found

Variant links:

Genes affected

ENSG00000253690 (HGNC:):

ENSG00000253690 links:

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:

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=-0.56).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNOC	XM_011544559.3 link	c.-240A>G		upstream_gene_variant			XP_011542861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253690	ENST00000521731.1 link	n.230+22189T>C		intron_variant	Intron 1 of 1	2
PNOC	ENST00000518479.5 link	c.-240A>G		upstream_gene_variant		4		ENSP00000428059.1		E7EVP0

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60934

AN:

151932

Hom.:

12650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.398

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.355

AC:

AN:

Hom.:

AF XY:

0.348

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.370

AC:

AN:

Other (OTH)

AF:

0.250

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

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:

0.401

AC:

60991

AN:

152050

Hom.:

12671

Cov.:

AF XY:

0.404

AC XY:

30009

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.474

AC:

19668

AN:

41462

American (AMR)

AF:

0.435

AC:

6641

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1380

AN:

3470

East Asian (EAS)

AF:

0.514

AC:

2653

AN:

5162

South Asian (SAS)

AF:

0.497

AC:

2392

AN:

4814

European-Finnish (FIN)

AF:

0.324

AC:

3430

AN:

10586

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.344

AC:

23393

AN:

67964

Other (OTH)

AF:

0.410

AC:

865

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1820

3640

5459

7279

9099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.368

Hom.:

10401

Bravo

AF:

0.411

Asia WGS

AF:

0.510

AC:

1770

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

2.3

PromoterAI

-0.030

Neutral

(source)

Splicing

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