Variant 18-50721934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002747.4(MAPK4):c.692-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00811 in 1,613,948 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 57 hom. )

Consequence

MAPK4
NM_002747.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001503

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.334

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 18-50721934-C-T is Benign according to our data. Variant chr18-50721934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648719.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 866 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK4	NM_002747.4 linkuse as main transcript	c.692-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000400384.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MAPK4	ENST00000400384.7 linkuse as main transcript	c.692-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_002747.4	P1
MAPK4	ENST00000592595.5 linkuse as main transcript	c.691+6711C>T	intron_variant	1
MAPK4	ENST00000540640.3 linkuse as main transcript	c.59-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00569

AC:

866

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00958

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00606

AC:

1508

AN:

248966

Hom.:

AF XY:

0.00620

AC XY:

837

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.00988

Gnomad OTH exome

AF:

0.00695

GnomAD4 exome

AF:

0.00836

AC:

12216

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

5864

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.00991

Gnomad4 OTH exome

AF:

0.00749

GnomAD4 genome

AF:

0.00568

AC:

866

AN:

152336

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00958

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00838

Hom.:

Bravo

AF:

0.00527

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.0103

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MAPK4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.7

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0060

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