rs3804452

Variant names:

• chr6-36109157-G-A
• rs3804452
• NM_139012.3:c.*710G>A

Variant summary

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

The NM_139012.3(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 NM_139012.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 28 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK14	NM_139012.3	MANE Select	c.*710G>A		3_prime_UTR	Exon 12 of 12	NP_620581.1	Q16539-1
	MAPK14	NM_001315.3		c.*710G>A		3_prime_UTR	Exon 12 of 12	NP_001306.1	L7RSM2
	MAPK14	NM_139014.3		c.*790G>A		3_prime_UTR	Exon 11 of 11	NP_620583.1	Q16539-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK14	ENST00000229794.9	TSL:1 MANE Select	c.*710G>A		3_prime_UTR	Exon 12 of 12	ENSP00000229794.4	Q16539-1
	MAPK14	ENST00000229795.8	TSL:1	c.*710G>A		3_prime_UTR	Exon 12 of 12	ENSP00000229795.3	Q16539-2
	MAPK14	ENST00000852146.1		c.*710G>A		3_prime_UTR	Exon 13 of 13	ENSP00000522205.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.105 AC: 45 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.118 AC: 18 AN: 152

Other (OTH) AF: 0.00 AC: 0 AN: 8

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

African (AFR) AF: 0.0281 AC: 1168 AN: 41554

American (AMR) AF: 0.0848 AC: 1298 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3470

East Asian (EAS) AF: 0.0527 AC: 273 AN: 5182

South Asian (SAS) AF: 0.102 AC: 491 AN: 4830

European-Finnish (FIN) AF: 0.140 AC: 1482 AN: 10590

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7515 AN: 68006

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.106 Hom.: 1189

Bravo AF: 0.0814

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.60
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3804452; hg19: chr6-36076934;