6-36039221-T-G

Variant names:

• chr6-36039221-T-G
• rs3804454
• NM_139012.3:c.116+10948T>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.116+10948T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,026 control chromosomes in the GnomAD database, including 4,089 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 0.23 (4089 hom., cov: 32)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 26 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK14	NM_139012.3	c.116+10948T>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.116+10948T>G		intron_variant	Intron 1 of 11	1	NM_139012.3	ENSP00000229794.4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35013 AN: 151908 Hom.: 4082 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.231 AC: 35043 AN: 152026 Hom.: 4089 Cov.: 32 AF XY: 0.230 AC XY: 17071 AN XY: 74326

African (AFR) AF: 0.285 AC: 11804 AN: 41432

American (AMR) AF: 0.180 AC: 2754 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3468

East Asian (EAS) AF: 0.181 AC: 936 AN: 5184

South Asian (SAS) AF: 0.168 AC: 808 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2350 AN: 10542

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14269 AN: 67984

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.215 Hom.: 12011

Bravo AF: 0.232

Asia WGS AF: 0.181 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3804454; hg19: chr6-36006998;