dbSNP rs3804452: MAPK14:c.*710G>A (chr6-36109157-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.530

Publications

28 publications found

Variant links:

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]

MAPK14 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK14	NM_139012.3 link	c.*710G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000229794.9	NP_620581.1	Q16539-1A0A024RD15

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAPK14	ENST00000229794.9 link	c.*710G>A	3_prime_UTR_variant	Exon 12 of 12	1	NM_139012.3	ENSP00000229794.4	Q16539-1
MAPK14	ENST00000229795.8 link	c.*710G>A	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000229795.3	Q16539-2
MAPK14	ENST00000718319.1 link	c.841+6508G>A	intron_variant	Intron 10 of 11			ENSP00000520753.1
MAPK14	ENST00000718318.1 link	c.841+6508G>A	intron_variant	Intron 10 of 10			ENSP00000520752.1

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13264

AN:

152132

Hom.:

707

Cov.:

show subpopulations

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:

AN:

612

Hom.:

Cov.:

AF XY:

0.0950

AC XY:

AN XY:

358

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.105

AC:

AN:

430

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.118

AC:

AN:

152

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0871

AC:

13263

AN:

152250

Hom.:

707

Cov.:

AF XY:

0.0882

AC XY:

6568

AN XY:

74438

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7515

AN:

68006

Other (OTH)

AF:

0.104

AC:

220

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

597

1193

1790

2386

2983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.82

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over