rs3804452

Positions:

• chr6-36109157-G-A

Variant summary

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

The ENST00000229794.9(MAPK14):​c.*710G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 152,862 control chromosomes in the GnomAD database, including 708 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 0.087 (707 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: MAPK14 ENST00000229794.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK14	NM_139012.3	c.*710G>A		3_prime_UTR_variant	12/12	ENST00000229794.9	NP_620581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK14	ENST00000229794.9	c.*710G>A		3_prime_UTR_variant	12/12	1	NM_139012.3	ENSP00000229794	P3
MAPK14	ENST00000229795.8	c.*710G>A		3_prime_UTR_variant	12/12	1		ENSP00000229795	A1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13264 AN: 152132 Hom.: 707 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.103 AC: 63 AN: 612 Hom.: 1 Cov.: 0 AF XY: 0.0950 AC XY: 34 AN XY: 358

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0871 AC: 13263 AN: 152250 Hom.: 707 Cov.: 32 AF XY: 0.0882 AC XY: 6568 AN XY: 74438

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.104

Alfa AF: 0.110 Hom.: 963

Bravo AF: 0.0814

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3804452; hg19: chr6-36076934;