rs12199654

Variant names:

• chr6-36041718-A-G
• rs12199654
• NM_139012.3:c.117-10981A>G

Variant summary

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

The NM_139012.3(MAPK14):​c.117-10981A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,322 control chromosomes in the GnomAD database, including 196 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 0.042 (196 hom., cov: 33)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 14 publications found

Genes affected

MAPK14 (HGNC:6876): (mitogen-activated protein kinase 14) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK14	NM_139012.3	c.117-10981A>G		intron_variant	Intron 1 of 11	ENST00000229794.9	NP_620581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK14	ENST00000229794.9	c.117-10981A>G		intron_variant	Intron 1 of 11	1	NM_139012.3	ENSP00000229794.4

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6437 AN: 152204 Hom.: 195 Cov.: 33

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0423 AC: 6436 AN: 152322 Hom.: 196 Cov.: 33 AF XY: 0.0432 AC XY: 3220 AN XY: 74482

African (AFR) AF: 0.0108 AC: 450 AN: 41580

American (AMR) AF: 0.0431 AC: 660 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.00443 AC: 23 AN: 5188

South Asian (SAS) AF: 0.0752 AC: 363 AN: 4824

European-Finnish (FIN) AF: 0.0516 AC: 548 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0601 AC: 4088 AN: 68020

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

Alfa AF: 0.0581 Hom.: 439

Bravo AF: 0.0391

Asia WGS AF: 0.0290 AC: 99 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.48
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: rs12199654; hg19: chr6-36009495;