Genetic Variant MAPK4:p.His61His (chr18-50664141-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002747.4(MAPK4):c.183C>T(p.His61His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,614,168 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 20 hom. )

Consequence

MAPK4
NM_002747.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.70

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 18-50664141-C-T is Benign according to our data. Variant chr18-50664141-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648718.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BS2

High AC in GnomAd4 at 644 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK4	NM_002747.4 link	c.183C>T	p.His61His	synonymous_variant	Exon 2 of 6	ENST00000400384.7	NP_002738.2	P31152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7 link	c.183C>T	p.His61His	synonymous_variant	Exon 2 of 6	1	NM_002747.4	ENSP00000383234.1		P31152

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

644

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00644

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00387

AC:

964

AN:

249370

Hom.:

AF XY:

0.00416

AC XY:

563

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00569

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00463

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00450

AC:

6577

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

3300

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00478

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00561

Gnomad4 FIN exome

AF:

0.00178

Gnomad4 NFE exome

AF:

0.00485

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.00423

AC:

644

AN:

152324

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00623

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00489

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00404

Hom.:

Bravo

AF:

0.00425

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00498

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAPK4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.24

DANN

Benign

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over