chr1-206716793-A-G

Variant names:

• chr1-206716793-A-G
• rs4548444
• NM_032960.4:c.280-11917A>G

Variant summary

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

The NM_032960.4(MAPKAPK2):​c.280-11917A>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 NM_032960.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 9 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=-0.9).
• 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 rank	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4	c.280-11917A>G		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.280-11917A>G		intron_variant	Intron 1 of 9	1	NM_032960.4	ENSP00000356070.4
MAPKAPK2	ENST00000294981.8	c.280-11917A>G		intron_variant	Intron 1 of 9	1		ENSP00000294981.4

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

African (AFR) AF: 0.117 AC: 4830 AN: 41358

American (AMR) AF: 0.281 AC: 4277 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3466

East Asian (EAS) AF: 0.287 AC: 1485 AN: 5176

South Asian (SAS) AF: 0.248 AC: 1189 AN: 4796

European-Finnish (FIN) AF: 0.252 AC: 2643 AN: 10480

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14859 AN: 67914

Other (OTH) AF: 0.246 AC: 517 AN: 2100

Alfa AF: 0.214 Hom.: 1906

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
PhyloP100		0.11
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: rs4548444; hg19: chr1-206890138;