rs12453363

Positions:

• chr17-50144555-G-A
• chr17-50144555-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032595.5(PPP1R9B):​c.1504+558C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,970 control chromosomes in the GnomAD database, including 2,345 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 0.17 (2345 hom., cov: 32)
• Consequence: PPP1R9B NM_032595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

Genes affected

PPP1R9B (HGNC:9298): (protein phosphatase 1 regulatory subunit 9B) This gene encodes a scaffold protein that functions as a regulatory subunit of protein phosphatase 1a. Expression of this gene is particularly high in dendritic spines, suggesting that the encoded protein may play a role in receiving signals from the central nervous system. The encoded protein has putative tumor suppressor function and decreased expression has been observed in tumors. [provided by RefSeq, Feb 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R9B	NM_032595.5	c.1504+558C>T		intron_variant		ENST00000612501.2	NP_115984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R9B	ENST00000612501.2	c.1504+558C>T		intron_variant		1	NM_032595.5	ENSP00000478767	P1
	ENST00000451776.1	n.209-568G>A		intron_variant, non_coding_transcript_variant		3
PPP1R9B	ENST00000513579.1	n.40+558C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25951 AN: 151852 Hom.: 2338 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.171 AC: 25970 AN: 151970 Hom.: 2345 Cov.: 32 AF XY: 0.168 AC XY: 12445 AN XY: 74276

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.172

Alfa AF: 0.162 Hom.: 2950

Bravo AF: 0.190

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.71

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: rs12453363; hg19: chr17-48221920; COSMIC: COSV57540864;