10-48386197-A-C

Variant names:

• chr10-48386197-A-C
• rs10857560
• NM_001323329.2:c.-49-15415A>C

Variant summary

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

The NM_001323329.2(MAPK8):​c.-49-15415A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,952 control chromosomes in the GnomAD database, including 19,929 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 0.50 (19929 hom., cov: 32)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323329.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	NM_001323329.2	MANE Select	c.-49-15415A>C		intron	N/A	NP_001310258.1
	MAPK8	NM_001278547.2		c.-49-15415A>C		intron	N/A	NP_001265476.1
	MAPK8	NM_001323322.2		c.-49-15415A>C		intron	N/A	NP_001310251.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.-49-15415A>C		intron	N/A	ENSP00000363304.1
	MAPK8	ENST00000374179.8	TSL:1	c.-49-15415A>C		intron	N/A	ENSP00000363294.3
	MAPK8	ENST00000395611.7	TSL:2	c.-49-15415A>C		intron	N/A	ENSP00000378974.4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76582 AN: 151834 Hom.: 19929 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.504 AC: 76607 AN: 151952 Hom.: 19929 Cov.: 32 AF XY: 0.504 AC XY: 37404 AN XY: 74252

African (AFR) AF: 0.374 AC: 15520 AN: 41444

American (AMR) AF: 0.489 AC: 7456 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2039 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3307 AN: 5164

South Asian (SAS) AF: 0.398 AC: 1913 AN: 4812

European-Finnish (FIN) AF: 0.554 AC: 5837 AN: 10544

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38684 AN: 67950

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.529 Hom.: 5470

Bravo AF: 0.501

Asia WGS AF: 0.484 AC: 1683 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.46
PhyloP100		2.0
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: rs10857560; hg19: chr10-49594240;