chr10-48411750-G-A

Variant names:

• chr10-48411750-G-A
• rs10857565
• NM_001323329.2:c.450+1582G>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.450+1582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,704 control chromosomes in the GnomAD database, including 2,977 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 0.19 (2977 hom., cov: 31)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK8	NM_001323329.2	c.450+1582G>A		intron_variant	Intron 5 of 11	ENST00000374189.6	NP_001310258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK8	ENST00000374189.6	c.450+1582G>A		intron_variant	Intron 5 of 11	5	NM_001323329.2	ENSP00000363304.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29056 AN: 151586 Hom.: 2973 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.192 AC: 29070 AN: 151704 Hom.: 2977 Cov.: 31 AF XY: 0.193 AC XY: 14315 AN XY: 74150

African (AFR) AF: 0.116 AC: 4791 AN: 41402

American (AMR) AF: 0.155 AC: 2359 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1319 AN: 5142

South Asian (SAS) AF: 0.287 AC: 1377 AN: 4796

European-Finnish (FIN) AF: 0.234 AC: 2464 AN: 10516

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15685 AN: 67852

Other (OTH) AF: 0.193 AC: 405 AN: 2102

Alfa AF: 0.138 Hom.: 348

Bravo AF: 0.179

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		0.42
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: rs10857565; hg19: chr10-49619793;