rs7146234

Variant names:

• chr14-60277916-A-G
• rs7146234
• NM_021003.5:c.-20-4768A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021003.5(PPM1A):​c.-20-4768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,026 control chromosomes in the GnomAD database, including 20,429 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 0.47 (20429 hom., cov: 32)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 8 publications found

Genes affected

PPM1A (HGNC:9275): (protein phosphatase, Mg2+/Mn2+ dependent 1A) 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 dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1A	NM_021003.5	c.-20-4768A>G		intron_variant	Intron 1 of 5	ENST00000395076.9	NP_066283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1A	ENST00000395076.9	c.-20-4768A>G		intron_variant	Intron 1 of 5	1	NM_021003.5	ENSP00000378514.4

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71247 AN: 151908 Hom.: 20386 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.469 AC: 71342 AN: 152026 Hom.: 20429 Cov.: 32 AF XY: 0.460 AC XY: 34212 AN XY: 74304

African (AFR) AF: 0.814 AC: 33728 AN: 41456

American (AMR) AF: 0.340 AC: 5190 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3470

East Asian (EAS) AF: 0.152 AC: 789 AN: 5176

South Asian (SAS) AF: 0.466 AC: 2242 AN: 4810

European-Finnish (FIN) AF: 0.275 AC: 2908 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23550 AN: 67964

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.389 Hom.: 21300

Bravo AF: 0.486

Asia WGS AF: 0.321 AC: 1118 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	3.6
DANN	Benign	0.51
PhyloP100		-0.36
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

Other links and lift over

dbSNP: rs7146234; hg19: chr14-60744634;