rs1551315

Positions:

• chr2-44180479-G-A

Variant summary

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

The NM_002706.6(PPM1B):​c.-15+11205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,232 control chromosomes in the GnomAD database, including 47,064 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 0.79 (47064 hom., cov: 33)
• Consequence: PPM1B NM_002706.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

Genes affected

PPM1B (HGNC:9276): (protein phosphatase, Mg2+/Mn2+ dependent 1B) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to cause cell-growth arrest or cell death. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional transcript variants have been described, but currently do not represent full-length sequences. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1B	NM_002706.6	c.-15+11205G>A		intron_variant		ENST00000282412.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1B	ENST00000282412.9	c.-15+11205G>A		intron_variant		1	NM_002706.6

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119461 AN: 152114 Hom.: 47028 Cov.: 33

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.785 AC: 119554 AN: 152232 Hom.: 47064 Cov.: 33 AF XY: 0.784 AC XY: 58317 AN XY: 74428

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.811

Alfa AF: 0.794 Hom.: 9701

Bravo AF: 0.785

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.75

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: rs1551315; hg19: chr2-44407618;