18-50664141-C-T

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

2

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]

Genome browser will be placed here

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
MAPK4NM_002747.4 linkc.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
MAPK4ENST00000400384.7 linkc.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.:
3
Cov.:
32
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.:
4
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.:
20
Cov.:
34
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.:
3
Cov.:
32
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.:
0
Bravo
AF:
0.00425
Asia WGS
AF:
0.00375
AC:
13
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.

Other links and lift over

dbSNP: rs55800528; hg19: chr18-48190511; API