dbSNP rs55800528: MAPK4:p.His61His (chr18-50664141-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002747.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK4	NM_002747.4	MANE Select	c.183C>T	p.His61His	synonymous	Exon 2 of 6	NP_002738.2	P31152
MAPK4	NM_001292040.2		c.183C>T	p.His61His	synonymous	Exon 2 of 4	NP_001278969.1	K7ELV1
MAPK4	NM_001292039.2		c.-87-50938C>T		intron	N/A	NP_001278968.1	B4DEW2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK4	ENST00000400384.7	TSL:1 MANE Select	c.183C>T	p.His61His	synonymous	Exon 2 of 6	ENSP00000383234.1	P31152
MAPK4	ENST00000588540.1	TSL:1	c.183C>T	p.His61His	synonymous	Exon 2 of 3	ENSP00000465661.1	K7EN18
MAPK4	ENST00000592595.5	TSL:1	c.183C>T	p.His61His	synonymous	Exon 2 of 4	ENSP00000466233.1	K7ELV1

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

GnomAD2 exomes

AF:

0.00387

AC:

964

AN:

249370

AF XY:

0.00416

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 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

African (AFR)

AF:

0.000627

AC:

AN:

33480

American (AMR)

AF:

0.00478

AC:

214

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00291

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00561

AC:

484

AN:

86258

European-Finnish (FIN)

AF:

0.00178

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00485

AC:

5389

AN:

1112006

Other (OTH)

AF:

0.00445

AC:

269

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

447

893

1340

1786

2233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00423

AC:

644

AN:

152324

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41572

American (AMR)

AF:

0.0123

AC:

189

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00623

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00489

AC:

333

AN:

68040

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00404

Hom.:

Bravo

AF:

0.00425

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00498

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.24

(source)

DANN

Benign

0.62

PhyloP100

-2.7

Mutation Taster

=96/4

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over