rs4488910

chr4-86441681-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.74).
• 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/exons	MANE	UniProt
MAPK10	NM_002753.6	c.-122+11349A>G		intron_variant
MAPK10	XM_047415964.1	c.36+152229A>G		intron_variant
MAPK10	XM_047415965.1	c.36+152229A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK10	ENST00000361569.8	c.-122+11349A>G		intron_variant		1
MAPK10	ENST00000395160.9	c.-122+11349A>G		intron_variant		1
MAPK10	ENST00000310816.8	c.-276+11349A>G		intron_variant, NMD_transcript_variant		1

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

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.153

Alfa AF: 0.153 Hom.: 3752

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4488910; hg19: chr4-87362834;