rs11779594

chr8-28324238-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006228.5(PNOC):c.-23-4897C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 152,270 control chromosomes in the GnomAD database, including 123 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 0.032 (123 hom., cov: 32)
• Consequence: PNOC NM_006228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0324 (4934/152270) while in subpopulation NFE AF= 0.048 (3268/68020). AF 95% confidence interval is 0.0467. There are 123 homozygotes in gnomad4. There are 2428 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNOC	NM_006228.5	c.-23-4897C>T		intron_variant		ENST00000301908.8
PNOC	XM_005273532.3	c.-23-4897C>T		intron_variant
PNOC	XM_011544559.3	c.-23-4897C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNOC	ENST00000301908.8	c.-23-4897C>T		intron_variant		1	NM_006228.5	P1
	ENST00000521731.1	n.230+14788G>A		intron_variant, non_coding_transcript_variant		2
PNOC	ENST00000518479.5	c.-23-4897C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4937 AN: 152152 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.00758

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0324 AC: 4934 AN: 152270 Hom.: 123 Cov.: 32 AF XY: 0.0326 AC XY: 2428 AN XY: 74444

Gnomad4 AFR AF: 0.00756

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0436 Hom.: 95

Bravo AF: 0.0281

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.2
Dann	Benign	0.43

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: rs11779594; hg19: chr8-28181755;