rs4129024

Positions:

• chr1-206694900-G-A

Variant summary

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

The ENST00000367103.4(MAPKAPK2):​c.279+9392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,272 control chromosomes in the GnomAD database, including 1,798 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 0.13 (1798 hom., cov: 32)
• Consequence: MAPKAPK2 ENST00000367103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

Genes affected

MAPKAPK2 (HGNC:6887): (MAPK activated protein kinase 2) This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4	c.279+9392G>A		intron_variant		ENST00000367103.4	NP_116584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK2	ENST00000367103.4	c.279+9392G>A		intron_variant		1	NM_032960.4	ENSP00000356070	P1
MAPKAPK2	ENST00000294981.8	c.279+9392G>A		intron_variant		1		ENSP00000294981

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20151 AN: 152154 Hom.: 1800 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.132 AC: 20149 AN: 152272 Hom.: 1798 Cov.: 32 AF XY: 0.130 AC XY: 9689 AN XY: 74456

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.158 Hom.: 365

Bravo AF: 0.121

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.025
DANN	Benign	0.46

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: rs4129024; hg19: chr1-206868245;