rs17010454

Variant names:

• chr10-48423545-A-G
• rs17010454
• NM_001323329.2:c.617-543A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139049.4(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_139049.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139049.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	NM_001323329.2	MANE Select	c.617-543A>G		intron	N/A	NP_001310258.1
	MAPK8	NM_001278547.2		c.617-969A>G		intron	N/A	NP_001265476.1
	MAPK8	NM_001323322.2		c.617-969A>G		intron	N/A	NP_001310251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.617-543A>G		intron	N/A	ENSP00000363304.1
	MAPK8	ENST00000374176.8	TSL:1	c.617-969A>G		intron	N/A	ENSP00000363291.4
	MAPK8	ENST00000374179.8	TSL:1	c.617-969A>G		intron	N/A	ENSP00000363294.3

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

African (AFR) AF: 0.0656 AC: 2729 AN: 41570

American (AMR) AF: 0.0355 AC: 543 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4824

European-Finnish (FIN) AF: 0.0334 AC: 355 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2704 AN: 68028

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0426 Hom.: 139

Bravo AF: 0.0446

Asia WGS AF: 0.00868 AC: 30 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.47
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17010454; hg19: chr10-49631588;