rs3730327

Positions:

• chr6-36059365-A-G

Variant summary

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

The NM_139012.3(MAPK14):​c.305+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,593,260 control chromosomes in the GnomAD database, including 11,534 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 0.16 (2697 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8837 hom.)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK14	NM_139012.3	c.305+18A>G		intron_variant		ENST00000229794.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK14	ENST00000229794.9	c.305+18A>G		intron_variant		1	NM_139012.3	P3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24427 AN: 152030 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.112 AC: 28208 AN: 251098 Hom.: 2100 AF XY: 0.109 AC XY: 14814 AN XY: 135740

Gnomad AFR exome AF: 0.326

Gnomad AMR exome AF: 0.0559

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0755

Gnomad NFE exome AF: 0.0982

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.102 AC: 147288 AN: 1441112 Hom.: 8837 Cov.: 26 AF XY: 0.102 AC XY: 73162 AN XY: 718168

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.0611

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0807

Gnomad4 NFE exome AF: 0.0955

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.161 AC: 24463 AN: 152148 Hom.: 2697 Cov.: 32 AF XY: 0.159 AC XY: 11813 AN XY: 74396

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.148

Alfa AF: 0.116 Hom.: 779

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.014
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3730327; hg19: chr6-36027142; COSMIC: COSV57696043;