1-206716793-A-G

Position:

• chr1-206716793-A-G

Variant summary

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

The ENST00000367103.4(MAPKAPK2):​c.280-11917A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,716 control chromosomes in the GnomAD database, including 3,318 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 0.20 (3318 hom., cov: 31)
• Consequence: MAPKAPK2 ENST00000367103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4	c.280-11917A>G		intron_variant		ENST00000367103.4	NP_116584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK2	ENST00000367103.4	c.280-11917A>G		intron_variant		1	NM_032960.4	ENSP00000356070	P1
MAPKAPK2	ENST00000294981.8	c.280-11917A>G		intron_variant		1		ENSP00000294981

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30889 AN: 151598 Hom.: 3318 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.204 AC: 30902 AN: 151716 Hom.: 3318 Cov.: 31 AF XY: 0.210 AC XY: 15558 AN XY: 74120

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.246

Alfa AF: 0.214 Hom.: 1714

Bravo AF: 0.199

Asia WGS AF: 0.270 AC: 940 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	0.98
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: rs4548444; hg19: chr1-206890138;