Genetic Variant MAPK14:c.762+1342T>C (chr6-36097408-T-C) – 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.762+1342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,062 control chromosomes in the GnomAD database, including 45,695 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 0.77 ( 45694 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

MAPK14
NM_139012.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.213

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 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	UniProt
MAPK14	NM_139012.3	MANE Select	c.762+1342T>C	intron	N/A	NP_620581.1	Q16539-1
MAPK14	NM_001315.3		c.683-2780T>C	intron	N/A	NP_001306.1	L7RSM2
MAPK14	NM_139014.3		c.762+1342T>C	intron	N/A	NP_620583.1	Q16539-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAPK14	ENST00000229794.9	TSL:1 MANE Select	c.762+1342T>C	intron	N/A	ENSP00000229794.4	Q16539-1
MAPK14	ENST00000229795.8	TSL:1	c.683-2780T>C	intron	N/A	ENSP00000229795.3	Q16539-2
MAPK14	ENST00000310795.8	TSL:1	c.762+1342T>C	intron	N/A	ENSP00000308669.4	Q16539-4

Frequencies

GnomAD3 genomes

AF:

0.773

AC:

117502

AN:

151942

Hom.:

45647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.802

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.944

Gnomad SAS

AF:

0.842

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.746

Gnomad OTH

AF:

0.753

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.773

AC:

117612

AN:

152060

Hom.:

45694

Cov.:

AF XY:

0.774

AC XY:

57562

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.803

AC:

33299

AN:

41482

American (AMR)

AF:

0.808

AC:

12346

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2456

AN:

3468

East Asian (EAS)

AF:

0.944

AC:

4882

AN:

5174

South Asian (SAS)

AF:

0.840

AC:

4049

AN:

4818

European-Finnish (FIN)

AF:

0.703

AC:

7416

AN:

10552

Middle Eastern (MID)

AF:

0.782

AC:

230

AN:

294

European-Non Finnish (NFE)

AF:

0.746

AC:

50684

AN:

67982

Other (OTH)

AF:

0.755

AC:

1589

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1387

2773

4160

5546

6933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.756

Hom.:

85457

Bravo

AF:

0.782

Asia WGS

AF:

0.881

AC:

3060

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

1.2

(source)

DANN

Benign

0.51

PhyloP100

-0.21

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