rs4478147

Positions:

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

Variant summary

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

The ENST00000513839.5(MAPK10):​c.-182+41287C>T variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK10	XM_047415964.1	c.36+41287C>T		intron_variant			XP_047271920.1
MAPK10	XM_047415965.1	c.36+41287C>T		intron_variant			XP_047271921.1
MAPK10	XM_047415966.1	c.36+41287C>T		intron_variant			XP_047271922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK10	ENST00000513839.5	c.-182+41287C>T		intron_variant, NMD_transcript_variant		1		ENSP00000492266
MAPK10	ENST00000502302.6	c.-263+41287C>T		intron_variant		4		ENSP00000423918
MAPK10	ENST00000512046.2	c.-122+41110C>T		intron_variant		3		ENSP00000492508

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

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.436

Alfa AF: 0.506 Hom.: 38555

Bravo AF: 0.394

Asia WGS AF: 0.638 AC: 2215 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4478147; hg19: chr4-87473776;