chr8-28340230-G-C

Variant names:

• chr8-28340230-G-C
• rs351784
• NM_006228.5:c.*47+739G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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]

ACMG classification

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111457 AN: 151948 Hom.: 42973 Cov.: 32

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: 79 AN: 90 Hom.: 34 Cov.: 0 AF XY: 0.871 AC XY: 61 AN XY: 70

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AF: 0.500 AC: 2 AN: 4

Gnomad4 SAS exome AF: 1.00 AC: 2 AN: 2

Gnomad4 FIN exome AF: 0.625 AC: 5 AN: 8

Gnomad4 NFE exome AF: 0.914 AC: 64 AN: 70

Gnomad4 Remaining exome AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.733 AC: 111497 AN: 152066 Hom.: 42977 Cov.: 32 AF XY: 0.731 AC XY: 54318 AN XY: 74348

Gnomad4 AFR AF: 0.483 AC: 0.483047 AN: 0.483047

Gnomad4 AMR AF: 0.780 AC: 0.77995 AN: 0.77995

Gnomad4 ASJ AF: 0.822 AC: 0.821614 AN: 0.821614

Gnomad4 EAS AF: 0.580 AC: 0.580364 AN: 0.580364

Gnomad4 SAS AF: 0.689 AC: 0.688797 AN: 0.688797

Gnomad4 FIN AF: 0.827 AC: 0.827166 AN: 0.827166

Gnomad4 NFE AF: 0.866 AC: 0.865731 AN: 0.865731

Gnomad4 OTH AF: 0.779 AC: 0.779092 AN: 0.779092

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
DANN	Benign	0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs351784; hg19: chr8-28197747;