rs1887103

Variant names:

• chr14-60276501-A-G
• rs1887103
• NM_021003.5:c.-20-6183A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-60276501-A-G
• chr14-60276501-A-T

Variant summary

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

The NM_021003.5(PPM1A):​c.-20-6183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,960 control chromosomes in the GnomAD database, including 20,548 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 (20548 hom., cov: 31)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1A	NM_021003.5	c.-20-6183A>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.-20-6183A>G		intron_variant	Intron 1 of 5	1	NM_021003.5	ENSP00000378514.4

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71518 AN: 151838 Hom.: 20505 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.471 AC: 71613 AN: 151960 Hom.: 20548 Cov.: 31 AF XY: 0.462 AC XY: 34328 AN XY: 74264

African (AFR) AF: 0.814 AC: 33782 AN: 41480

American (AMR) AF: 0.343 AC: 5228 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3468

East Asian (EAS) AF: 0.153 AC: 789 AN: 5170

South Asian (SAS) AF: 0.467 AC: 2243 AN: 4806

European-Finnish (FIN) AF: 0.277 AC: 2919 AN: 10550

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.349 AC: 23716 AN: 67916

Other (OTH) AF: 0.455 AC: 960 AN: 2108

Alfa AF: 0.440 Hom.: 3385

Bravo AF: 0.488

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	-0.90
CADD	Benign	2.3
DANN	Benign	0.79
PhyloP100		-0.39
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: rs1887103; hg19: chr14-60743219;