rs10857561

chr10-48400595-G-A

Variant summary

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

The NM_001323329.2(MAPK8):c.-49-1017G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,006 control chromosomes in the GnomAD database, including 6,643 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 0.29 (6643 hom., cov: 32)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.-49-1017G>A		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.-49-1017G>A		intron_variant		5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43768 AN: 151888 Hom.: 6638 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.288 AC: 43789 AN: 152006 Hom.: 6643 Cov.: 32 AF XY: 0.291 AC XY: 21627 AN XY: 74318

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.279

Alfa AF: 0.326 Hom.: 16898

Bravo AF: 0.270

Asia WGS AF: 0.345 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.5
Dann	Benign	0.57

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: rs10857561; hg19: chr10-49608638;