rs10857561

Variant names:

• chr10-48400595-G-A
• rs10857561
• NM_001323329.2:c.-49-1017G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.82).
• 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 rank	MANE	Protein	UniProt
MAPK8	NM_001323329.2	c.-49-1017G>A		intron_variant	Intron 1 of 11	ENST00000374189.6	NP_001310258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK8	ENST00000374189.6	c.-49-1017G>A		intron_variant	Intron 1 of 11	5	NM_001323329.2	ENSP00000363304.1

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

African (AFR) AF: 0.193 AC: 7981 AN: 41434

American (AMR) AF: 0.226 AC: 3456 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1633 AN: 5168

South Asian (SAS) AF: 0.393 AC: 1893 AN: 4814

European-Finnish (FIN) AF: 0.372 AC: 3925 AN: 10564

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23051 AN: 67958

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.317 Hom.: 25296

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
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10857561; hg19: chr10-49608638;