Genetic Variant NM_139012.3:c.*1956C>T (chr6-36110403-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_139012.3(MAPK14):c.*1956C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,714 control chromosomes in the GnomAD database, including 1,671 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 0.11 ( 1667 hom., cov: 33)

Exomes 𝑓: 0.15 ( 4 hom. )

Consequence

MAPK14
NM_139012.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

21 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAPK14	NM_139012.3	MANE Select	c.*1956C>T	3_prime_UTR	Exon 12 of 12	NP_620581.1
MAPK14	NM_001315.3		c.*1956C>T	3_prime_UTR	Exon 12 of 12	NP_001306.1
MAPK14	NM_139014.3		c.*2036C>T	3_prime_UTR	Exon 11 of 11	NP_620583.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAPK14	ENST00000229794.9	TSL:1 MANE Select	c.*1956C>T	3_prime_UTR	Exon 12 of 12	ENSP00000229794.4
MAPK14	ENST00000229795.8	TSL:1	c.*1956C>T	3_prime_UTR	Exon 12 of 12	ENSP00000229795.3
MAPK14	ENST00000718319.1		c.842-5956C>T	intron	N/A	ENSP00000520753.1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16252

AN:

152160

Hom.:

1658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.0770

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.0902

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0913

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.147

AC:

AN:

436

Hom.:

Cov.:

AF XY:

0.149

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.143

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.107

AC:

16272

AN:

152278

Hom.:

1667

Cov.:

AF XY:

0.112

AC XY:

8360

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0337

AC:

1400

AN:

41566

American (AMR)

AF:

0.224

AC:

3419

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0770

AC:

267

AN:

3466

East Asian (EAS)

AF:

0.506

AC:

2622

AN:

5178

South Asian (SAS)

AF:

0.0896

AC:

433

AN:

4832

European-Finnish (FIN)

AF:

0.151

AC:

1604

AN:

10610

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0913

AC:

6213

AN:

68018

Other (OTH)

AF:

0.108

AC:

229

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

685

1371

2056

2742

3427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0948

Hom.:

413

Bravo

AF:

0.116

Asia WGS

AF:

0.263

AC:

910

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over