1-206694900-G-A

Variant names:

• chr1-206694900-G-A
• rs4129024
• NM_032960.4:c.279+9392G>A

Variant summary

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

The NM_032960.4(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 NM_032960.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4	c.279+9392G>A		intron_variant	Intron 1 of 9	ENST00000367103.4	NP_116584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPKAPK2	ENST00000367103.4	c.279+9392G>A		intron_variant	Intron 1 of 9	1	NM_032960.4	ENSP00000356070.4
MAPKAPK2	ENST00000294981.8	c.279+9392G>A		intron_variant	Intron 1 of 9	1		ENSP00000294981.4

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

African (AFR) AF: 0.0359 AC: 1493 AN: 41570

American (AMR) AF: 0.106 AC: 1628 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5188

South Asian (SAS) AF: 0.0956 AC: 461 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1957 AN: 10596

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13926 AN: 68010

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

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
PhyloP100		-0.92
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: rs4129024; hg19: chr1-206868245;