rs11726269

Positions:

• chr4-86311831-A-G

Variant summary

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

The NM_138982.4(MAPK10):​c.-7+42699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,174 control chromosomes in the GnomAD database, including 463 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 0.069 (463 hom., cov: 32)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

Genes affected

MAPK10 (HGNC:6872): (mitogen-activated protein kinase 10) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK10	NM_138982.4	c.-7+42699T>C		intron_variant		ENST00000641462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK10	ENST00000641462.2	c.-7+42699T>C		intron_variant			NM_138982.4	P4

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10436 AN: 152056 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0686 AC: 10433 AN: 152174 Hom.: 463 Cov.: 32 AF XY: 0.0664 AC XY: 4942 AN XY: 74398

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.0945

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0889 Hom.: 294

Bravo AF: 0.0653

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.3
DANN	Benign	0.57

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: rs11726269; hg19: chr4-87232984;