rs4488910

Variant names:

• chr4-86441681-T-C
• rs4488910
• ENST00000395160.9:c.-122+11349A>G

Variant summary

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

The ENST00000395160.9(MAPK10):​c.-122+11349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,156 control chromosomes in the GnomAD database, including 1,840 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 0.15 (1840 hom., cov: 32)
• Consequence: MAPK10 ENST00000395160.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 11 publications found

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]

MAPK10 Gene-Disease associations (from GenCC):

• Lennox-Gastaut syndrome

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_002753.6	c.-122+11349A>G		intron_variant	Intron 1 of 13		NP_002744.1
MAPK10	XM_047415964.1	c.36+152229A>G		intron_variant	Intron 1 of 12		XP_047271920.1
MAPK10	XM_047415965.1	c.36+152229A>G		intron_variant	Intron 1 of 7		XP_047271921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK10	ENST00000395160.9	c.-122+11349A>G		intron_variant	Intron 1 of 13	1		ENSP00000378589.5
MAPK10	ENST00000361569.8	c.-122+11349A>G		intron_variant	Intron 1 of 13	1		ENSP00000355297.3
MAPK10	ENST00000310816.8	n.-276+11349A>G		intron_variant	Intron 1 of 13	1		ENSP00000309857.4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22927 AN: 152040 Hom.: 1837 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.151 AC: 22958 AN: 152156 Hom.: 1840 Cov.: 32 AF XY: 0.151 AC XY: 11204 AN XY: 74386

African (AFR) AF: 0.145 AC: 6011 AN: 41504

American (AMR) AF: 0.156 AC: 2377 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5182

South Asian (SAS) AF: 0.176 AC: 847 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10596

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10077 AN: 68000

Other (OTH) AF: 0.153 AC: 323 AN: 2108

Alfa AF: 0.152 Hom.: 7680

Bravo AF: 0.153

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.63
DANN	Benign	0.68
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4488910; hg19: chr4-87362834;