chr17-39634528-T-C

Variant names:

• chr17-39634528-T-C
• rs3764353
• NM_032192.4:c.445+442T>C

Variant summary

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

The NM_032192.4(PPP1R1B):​c.445+442T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,120 control chromosomes in the GnomAD database, including 31,377 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 0.60 (31377 hom., cov: 33)
• Consequence: PPP1R1B NM_032192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 8 publications found

Genes affected

PPP1R1B (HGNC:9287): (protein phosphatase 1 regulatory inhibitor subunit 1B) This gene encodes a bifunctional signal transduction molecule. Dopaminergic and glutamatergic receptor stimulation regulates its phosphorylation and function as a kinase or phosphatase inhibitor. As a target for dopamine, this gene may serve as a therapeutic target for neurologic and psychiatric disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ENSG00000306162 (HGNC:):

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 = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R1B	NM_032192.4	c.445+442T>C		intron_variant	Intron 5 of 6	ENST00000254079.9	NP_115568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R1B	ENST00000254079.9	c.445+442T>C		intron_variant	Intron 5 of 6	1	NM_032192.4	ENSP00000254079.4

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91691 AN: 152002 Hom.: 31372 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.603 AC: 91714 AN: 152120 Hom.: 31377 Cov.: 33 AF XY: 0.602 AC XY: 44786 AN XY: 74372

African (AFR) AF: 0.272 AC: 11303 AN: 41484

American (AMR) AF: 0.612 AC: 9352 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2561 AN: 3466

East Asian (EAS) AF: 0.442 AC: 2280 AN: 5158

South Asian (SAS) AF: 0.724 AC: 3496 AN: 4832

European-Finnish (FIN) AF: 0.778 AC: 8239 AN: 10590

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52253 AN: 67984

Other (OTH) AF: 0.634 AC: 1338 AN: 2112

Alfa AF: 0.605 Hom.: 4644

Bravo AF: 0.575

Asia WGS AF: 0.612 AC: 2131 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	6.7
DANN	Benign	0.57
PhyloP100		0.18
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

Other links and lift over

dbSNP: rs3764353; hg19: chr17-37790781; COSMIC: COSV54203236; COSMIC: COSV54203236;