rs7221274

chr17-58930767-A-G

Variant summary

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

The NM_014906.5(PPM1E):c.465-24882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,980 control chromosomes in the GnomAD database, including 11,053 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 0.38 (11053 hom., cov: 31)
• Consequence: PPM1E NM_014906.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

Genes affected

PPM1E (HGNC:19322): (protein phosphatase, Mg2+/Mn2+ dependent 1E) This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1E	NM_014906.5	c.465-24882A>G		intron_variant		ENST00000308249.4
PPM1E	XM_024450657.2	c.-253-24882A>G		intron_variant
PPM1E	XM_047435630.1	c.-47-24882A>G		intron_variant
PPM1E	NR_048561.1	n.594-24882A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1E	ENST00000308249.4	c.465-24882A>G		intron_variant		1	NM_014906.5	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57356 AN: 151862 Hom.: 11051 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.378 AC: 57378 AN: 151980 Hom.: 11053 Cov.: 31 AF XY: 0.375 AC XY: 27894 AN XY: 74292

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.409

Alfa AF: 0.400 Hom.: 25191

Bravo AF: 0.371

Asia WGS AF: 0.367 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.4
Dann	Benign	0.54

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: rs7221274; hg19: chr17-57008128;