rs17010454

Positions:

• chr10-48423545-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323329.2(MAPK8):​c.617-543A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 152,314 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.044 (167 hom., cov: 32)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.617-543A>G		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.617-543A>G		intron_variant		5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6659 AN: 152196 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0438 AC: 6664 AN: 152314 Hom.: 167 Cov.: 32 AF XY: 0.0418 AC XY: 3113 AN XY: 74484

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.0355

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0334

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0427 Hom.: 120

Bravo AF: 0.0446

Asia WGS AF: 0.00868 AC: 30 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs17010454; hg19: chr10-49631588;