Variant rs3752087 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002747.4(MAPK4):c.112G>A(p.Val38Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,580 control chromosomes in the GnomAD database, including 124,988 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.33 ( 9140 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115848 hom. )

Consequence

MAPK4
NM_002747.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.144

Variant links:

Genes affected

MAPK4 (HGNC:6878): (mitogen-activated protein kinase 4) Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

MAPK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.6383014E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK4	NM_002747.4 linkuse as main transcript	c.112G>A	p.Val38Met	missense_variant	2/6	ENST00000400384.7	NP_002738.2	P31152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAPK4	ENST00000400384.7 linkuse as main transcript	c.112G>A	p.Val38Met	missense_variant	2/6	1	NM_002747.4	ENSP00000383234.1	P31152
MAPK4	ENST00000588540.1 linkuse as main transcript	c.112G>A	p.Val38Met	missense_variant	2/3	1		ENSP00000465661.1	K7EN18
MAPK4	ENST00000592595.5 linkuse as main transcript	c.112G>A	p.Val38Met	missense_variant	2/4	1		ENSP00000466233.1	K7ELV1
MAPK4	ENST00000540640.3 linkuse as main transcript	c.-87-51009G>A		intron_variant		2		ENSP00000439231.1	B4DEW2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49673

AN:

151936

Hom.:

9139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.396

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.364

GnomAD3 exomes

AF:

0.366

AC:

91131

AN:

249292

Hom.:

17854

AF XY:

0.377

AC XY:

50930

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.388

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.394

AC:

575847

AN:

1461528

Hom.:

115848

Cov.:

AF XY:

0.396

AC XY:

287819

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.416

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.386

GnomAD4 genome

AF:

0.327

AC:

49671

AN:

152052

Hom.:

9140

Cov.:

AF XY:

0.330

AC XY:

24509

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.396

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.402

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.393

Hom.:

29507

Bravo

AF:

0.305

TwinsUK

AF:

0.426

AC:

1579

ALSPAC

AF:

0.408

AC:

1574

ESP6500AA

AF:

0.154

AC:

650

ESP6500EA

AF:

0.395

AC:

3335

ExAC

AF:

0.365

AC:

44140

Asia WGS

AF:

0.363

AC:

1263

AN:

3478

EpiCase

AF:

0.404

EpiControl

AF:

0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.023

T;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.00056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.89

L;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.97

N;.;.

REVEL

Benign

0.14

Sift

Benign

0.13

T;.;.

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.94

P;.;.

Vest4

0.038

MPC

0.61

ClinPred

0.030

GERP RS

-4.1

Varity_R

0.11

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over