rs4478147

Variant names:

• chr4-86552623-G-A
• rs4478147
• ENST00000513839.5:n.-182+41287C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-86552623-G-A
• chr4-86552623-G-C

Variant summary

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

The ENST00000513839.5(MAPK10):​n.-182+41287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,814 control chromosomes in the GnomAD database, including 15,729 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 0.42 (15729 hom., cov: 30)
• Consequence: MAPK10 ENST00000513839.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 12 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513839.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	ENST00000513839.5	TSL:1	n.-182+41287C>T		intron	N/A	ENSP00000492266.1
	MAPK10	ENST00000515400.3	TSL:5	c.-159+41287C>T		intron	N/A	ENSP00000424154.3
	MAPK10	ENST00000641051.1		c.-274+41287C>T		intron	N/A	ENSP00000493275.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63877 AN: 151696 Hom.: 15726 Cov.: 30

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.421 AC: 63897 AN: 151814 Hom.: 15729 Cov.: 30 AF XY: 0.429 AC XY: 31820 AN XY: 74204

African (AFR) AF: 0.154 AC: 6395 AN: 41414

American (AMR) AF: 0.434 AC: 6631 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1896 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3019 AN: 5148

South Asian (SAS) AF: 0.702 AC: 3373 AN: 4802

European-Finnish (FIN) AF: 0.557 AC: 5846 AN: 10502

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35259 AN: 67916

Other (OTH) AF: 0.436 AC: 916 AN: 2102

Alfa AF: 0.493 Hom.: 78752

Bravo AF: 0.394

Asia WGS AF: 0.638 AC: 2215 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.41
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs4478147; hg19: chr4-87473776;