Variant 10-48426136-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001323329.2(MAPK8):c.871+66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,320,640 control chromosomes in the GnomAD database, including 4,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.061 ( 623 hom., cov: 32)

Exomes 𝑓: 0.058 ( 3387 hom. )

Consequence

MAPK8
NM_001323329.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.220

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-48426136-G-A is Benign according to our data. Variant chr10-48426136-G-A is described in ClinVar as [Benign]. Clinvar id is 2688159.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 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.871+66G>A		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6 linkuse as main transcript	c.871+66G>A		intron_variant		5	NM_001323329.2	A1	P45983-1

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

9287

AN:

151706

Hom.:

623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0275

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0417

Gnomad MID

AF:

0.0353

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0637

GnomAD4 exome

AF:

0.0585

AC:

68338

AN:

1168814

Hom.:

3387

Cov.:

AF XY:

0.0601

AC XY:

34973

AN XY:

581502

show subpopulations

Gnomad4 AFR exome

AF:

0.0258

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.0168

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0471

Gnomad4 NFE exome

AF:

0.0477

Gnomad4 OTH exome

AF:

0.0630

GnomAD4 genome

AF:

0.0613

AC:

9303

AN:

151826

Hom.:

623

Cov.:

AF XY:

0.0663

AC XY:

4919

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.0276

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.0417

Gnomad4 NFE

AF:

0.0460

Gnomad4 OTH

AF:

0.0664

Alfa

AF:

0.0536

Hom.:

Bravo

AF:

0.0686

Asia WGS

AF:

0.120

AC:

415

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.85

CADD

Benign

3.9

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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