chr1-206723277-C-A

Variant names:

• chr1-206723277-C-A
• rs4240847
• NM_032960.4:c.280-5433C>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.280-5433C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,112 control chromosomes in the GnomAD database, including 43,553 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 0.75 (43553 hom., cov: 32)
• Consequence: MAPKAPK2 NM_032960.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 13 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 (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032960.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK2	NM_032960.4	MANE Select	c.280-5433C>A		intron	N/A	NP_116584.2
	MAPKAPK2	NM_004759.5		c.280-5433C>A		intron	N/A	NP_004750.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK2	ENST00000367103.4	TSL:1 MANE Select	c.280-5433C>A		intron	N/A	ENSP00000356070.4
	MAPKAPK2	ENST00000294981.8	TSL:1	c.280-5433C>A		intron	N/A	ENSP00000294981.4
	MAPKAPK2	ENST00000916346.1		c.280-5433C>A		intron	N/A	ENSP00000586405.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114601 AN: 151994 Hom.: 43511 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.754 AC: 114698 AN: 152112 Hom.: 43553 Cov.: 32 AF XY: 0.759 AC XY: 56406 AN XY: 74350

African (AFR) AF: 0.672 AC: 27832 AN: 41436

American (AMR) AF: 0.824 AC: 12603 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 3000 AN: 3472

East Asian (EAS) AF: 0.899 AC: 4639 AN: 5162

South Asian (SAS) AF: 0.821 AC: 3961 AN: 4826

European-Finnish (FIN) AF: 0.800 AC: 8480 AN: 10600

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51639 AN: 68008

Other (OTH) AF: 0.802 AC: 1694 AN: 2112

Alfa AF: 0.769 Hom.: 120062

Bravo AF: 0.754

Asia WGS AF: 0.847 AC: 2943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		-0.034
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: rs4240847; hg19: chr1-206896622;