NM_032192.4:c.82-433G>A

Variant names:

• chr17-39628737-G-A
• rs2271309
• NM_032192.4:c.82-433G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R1B	NM_032192.4	MANE Select	c.82-433G>A		intron	N/A	NP_115568.2
	PPP1R1B	NM_001242464.2		c.-28+115G>A		intron	N/A	NP_001229393.1	Q9UD71-2
	PPP1R1B	NM_181505.4		c.-28+31G>A		intron	N/A	NP_852606.1	Q9UD71-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R1B	ENST00000254079.9	TSL:1 MANE Select	c.82-433G>A		intron	N/A	ENSP00000254079.4	Q9UD71-1
	PPP1R1B	ENST00000394265.5	TSL:1	c.-28+115G>A		intron	N/A	ENSP00000377808.1	Q9UD71-2
	PPP1R1B	ENST00000394267.2	TSL:1	c.-28+31G>A		intron	N/A	ENSP00000377810.2	Q9UD71-2

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

African (AFR) AF: 0.252 AC: 3985 AN: 15790

American (AMR) AF: 0.641 AC: 1343 AN: 2094

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 3953 AN: 5374

East Asian (EAS) AF: 0.433 AC: 1665 AN: 3844

South Asian (SAS) AF: 0.758 AC: 13791 AN: 18182

European-Finnish (FIN) AF: 0.785 AC: 634 AN: 808

Middle Eastern (MID) AF: 0.788 AC: 1314 AN: 1668

European-Non Finnish (NFE) AF: 0.787 AC: 603113 AN: 766554

Other (OTH) AF: 0.734 AC: 20384 AN: 27770

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

African (AFR) AF: 0.276 AC: 11474 AN: 41514

American (AMR) AF: 0.613 AC: 9387 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2567 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2280 AN: 5170

South Asian (SAS) AF: 0.722 AC: 3486 AN: 4826

European-Finnish (FIN) AF: 0.778 AC: 8253 AN: 10602

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52277 AN: 67970

Other (OTH) AF: 0.634 AC: 1341 AN: 2114

Alfa AF: 0.650 Hom.: 4525

Bravo AF: 0.577

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.56
PhyloP100		-1.0
PromoterAI		0.0041	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2271309;

hg19: chr17-37784990;