rs7440491

Variant names:

• chr4-86162886-C-A
• rs7440491
• NM_138982.4:c.67-3419G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-86162886-C-A
• chr4-86162886-C-G
• chr4-86162886-C-T

Variant summary

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

The NM_138982.4(MAPK10):​c.67-3419G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,944 control chromosomes in the GnomAD database, including 37,622 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 0.67 (37622 hom., cov: 32)
• Consequence: MAPK10 NM_138982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 3 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-AS1 (HGNC:40359): (MAPK10 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138982.4. 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
	MAPK10	NM_138982.4	MANE Select	c.67-3419G>T		intron	N/A	NP_620448.1
	MAPK10	NM_001318069.2		c.67-3419G>T		intron	N/A	NP_001304998.1
	MAPK10	NM_001318067.1		c.67-3419G>T		intron	N/A	NP_001304996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK10	ENST00000641462.2	MANE Select	c.67-3419G>T		intron	N/A	ENSP00000493435.1
	MAPK10	ENST00000638225.1	TSL:1	c.-48-3419G>T		intron	N/A	ENSP00000491866.1
	MAPK10	ENST00000395160.9	TSL:1	c.67-3419G>T		intron	N/A	ENSP00000378589.5

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102438 AN: 151826 Hom.: 37617 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.674 AC: 102458 AN: 151944 Hom.: 37622 Cov.: 32 AF XY: 0.681 AC XY: 50569 AN XY: 74270

African (AFR) AF: 0.358 AC: 14849 AN: 41428

American (AMR) AF: 0.760 AC: 11588 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2363 AN: 3470

East Asian (EAS) AF: 0.919 AC: 4749 AN: 5166

South Asian (SAS) AF: 0.793 AC: 3823 AN: 4822

European-Finnish (FIN) AF: 0.844 AC: 8930 AN: 10582

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53631 AN: 67914

Other (OTH) AF: 0.691 AC: 1459 AN: 2112

Alfa AF: 0.747 Hom.: 57471

Bravo AF: 0.656

Asia WGS AF: 0.825 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.051
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7440491; hg19: chr4-87084039;