17-39634528-T-C

Position:

• chr17-39634528-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPP1R1B	NM_032192.4	c.445+442T>C		intron_variant		ENST00000254079.9	NP_115568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R1B	ENST00000254079.9	c.445+442T>C		intron_variant		1	NM_032192.4	ENSP00000254079	P1

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.634

Alfa AF: 0.617 Hom.: 4613

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

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