Variant 10-48404801-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001323329.2(MAPK8):c.123-51A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 1,465,298 control chromosomes in the GnomAD database, including 4,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 610 hom., cov: 31)

Exomes 𝑓: 0.059 ( 4025 hom. )

Consequence

MAPK8
NM_001323329.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.735

Variant links:

Genes affected

MAPK8 (HGNC:6881): (mitogen-activated protein kinase 8) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

MAPK8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-48404801-A-C is Benign according to our data. Variant chr10-48404801-A-C is described in ClinVar as [Benign]. Clinvar id is 1223363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2 linkuse as main transcript	c.123-51A>C		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6 linkuse as main transcript	c.123-51A>C		intron_variant		5	NM_001323329.2	A1	P45983-1

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8830

AN:

152132

Hom.:

610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.0652

Gnomad EAS

AF:

0.0275

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0413

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0618

GnomAD3 exomes

AF:

0.0849

AC:

18235

AN:

214746

Hom.:

1679

AF XY:

0.0821

AC XY:

9598

AN XY:

116888

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.0696

Gnomad EAS exome

AF:

0.0282

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0421

Gnomad NFE exome

AF:

0.0446

Gnomad OTH exome

AF:

0.0769

GnomAD4 exome

AF:

0.0590

AC:

77413

AN:

1313048

Hom.:

4025

Cov.:

AF XY:

0.0611

AC XY:

40091

AN XY:

656134

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.0701

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.0464

Gnomad4 NFE exome

AF:

0.0470

Gnomad4 OTH exome

AF:

0.0615

GnomAD4 genome

AF:

0.0581

AC:

8840

AN:

152250

Hom.:

610

Cov.:

AF XY:

0.0631

AC XY:

4699

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.0652

Gnomad4 EAS

AF:

0.0276

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.0413

Gnomad4 NFE

AF:

0.0460

Gnomad4 OTH

AF:

0.0645

Alfa

AF:

0.0526

Hom.:

Bravo

AF:

0.0652

Asia WGS

AF:

0.119

AC:

413

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.59

DANN

Benign

0.63

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