rs2271309

Positions:

• chr17-39628737-G-A
• chr17-39628737-G-T

Variant summary

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

The NM_032192.4(PPP1R1B):​c.82-433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 994,260 control chromosomes in the GnomAD database, including 285,255 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 (31457 hom., cov: 33)
  • Exomes 𝑓: 0.77 (253798 hom.)
• Consequence: PPP1R1B NM_032192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R1B	NM_032192.4	c.82-433G>A		intron_variant		ENST00000254079.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R1B	ENST00000254079.9	c.82-433G>A		intron_variant		1	NM_032192.4	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91924 AN: 152058 Hom.: 31450 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.772 AC: 650182 AN: 842084 Hom.: 253798 Cov.: 18 AF XY: 0.773 AC XY: 301502 AN XY: 389982

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.734

GnomAD4 genome AF: 0.604 AC: 91952 AN: 152176 Hom.: 31457 Cov.: 33 AF XY: 0.603 AC XY: 44893 AN XY: 74394

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.634

Alfa AF: 0.666 Hom.: 4494

Bravo AF: 0.577

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.56

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: rs2271309; hg19: chr17-37784990;