NM_001323329.2:c.-50+5139A>G

Variant names:

• chr10-48311960-A-G
• rs1919709
• NM_001323329.2:c.-50+5139A>G

Variant summary

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

The NM_001323329.2(MAPK8):​c.-50+5139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,222 control chromosomes in the GnomAD database, including 52,901 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 0.83 (52901 hom., cov: 32)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK8	NM_001323329.2	c.-50+5139A>G		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.-50+5139A>G		intron_variant	Intron 1 of 11	5	NM_001323329.2	ENSP00000363304.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126145 AN: 152104 Hom.: 52842 Cov.: 32

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.829 AC: 126260 AN: 152222 Hom.: 52901 Cov.: 32 AF XY: 0.827 AC XY: 61569 AN XY: 74422

African (AFR) AF: 0.958 AC: 39793 AN: 41548

American (AMR) AF: 0.852 AC: 13035 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2929 AN: 3470

East Asian (EAS) AF: 0.743 AC: 3846 AN: 5174

South Asian (SAS) AF: 0.713 AC: 3440 AN: 4828

European-Finnish (FIN) AF: 0.765 AC: 8106 AN: 10594

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52297 AN: 68002

Other (OTH) AF: 0.823 AC: 1739 AN: 2112

Alfa AF: 0.810 Hom.: 7323

Bravo AF: 0.846

Asia WGS AF: 0.728 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.52
PhyloP100		-2.7
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: rs1919709; hg19: chr10-49520003;