Variant 10-48409974-A-G 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.311+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 1,607,790 control chromosomes in the GnomAD database, including 5,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 617 hom., cov: 32)

Exomes 𝑓: 0.060 ( 4615 hom. )

Consequence

MAPK8
NM_001323329.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.145

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-48409974-A-G is Benign according to our data. Variant chr10-48409974-A-G is described in ClinVar as [Benign]. Clinvar id is 1259128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 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.311+37A>G		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6 linkuse as main transcript	c.311+37A>G		intron_variant		5	NM_001323329.2	A1	P45983-1

Frequencies

GnomAD3 genomes

AF:

0.0583

AC:

8864

AN:

152128

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0618

GnomAD3 exomes

AF:

0.0905

AC:

22209

AN:

245450

Hom.:

2110

AF XY:

0.0875

AC XY:

11584

AN XY:

132448

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.0698

Gnomad EAS exome

AF:

0.0285

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0420

Gnomad NFE exome

AF:

0.0451

Gnomad OTH exome

AF:

0.0800

GnomAD4 exome

AF:

0.0596

AC:

86735

AN:

1455544

Hom.:

4615

Cov.:

AF XY:

0.0616

AC XY:

44552

AN XY:

723742

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.0709

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.0463

Gnomad4 NFE exome

AF:

0.0467

Gnomad4 OTH exome

AF:

0.0620

GnomAD4 genome

AF:

0.0583

AC:

8874

AN:

152246

Hom.:

617

Cov.:

AF XY:

0.0635

AC XY:

4727

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.0273

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0460

Gnomad4 OTH

AF:

0.0645

Alfa

AF:

0.0538

Hom.:

Bravo

AF:

0.0653

Asia WGS

AF:

0.120

AC:

417

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 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.3

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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