chr10-48434548-A-C

Position:

• chr10-48434548-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323329.2(MAPK8):​c.1139-336A>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 152,022 control chromosomes in the GnomAD database, including 19,910 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 (19910 hom., cov: 32)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849

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]

ARHGAP22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK8	NM_001323329.2	c.1139-336A>C		intron_variant		ENST00000374189.6	NP_001310258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8	ENST00000374189.6	c.1139-336A>C		intron_variant		5	NM_001323329.2	ENSP00000363304	A1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76580 AN: 151904 Hom.: 19910 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.504 AC: 76605 AN: 152022 Hom.: 19910 Cov.: 32 AF XY: 0.504 AC XY: 37433 AN XY: 74328

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.533

Alfa AF: 0.384 Hom.: 1030

Bravo AF: 0.501

Asia WGS AF: 0.485 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs4838590; hg19: chr10-49642591;