rs10432016

Positions:

• chr17-12087362-A-G
• chr17-12087362-A-T

Variant summary

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

The NM_003010.4(MAP2K4):​c.393+5832A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,928 control chromosomes in the GnomAD database, including 16,802 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 0.46 (16802 hom., cov: 31)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788

Genes affected

MAP2K4 (HGNC:6844): (mitogen-activated protein kinase kinase 4) This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K4	NM_003010.4	c.393+5832A>G		intron_variant		ENST00000353533.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K4	ENST00000353533.10	c.393+5832A>G		intron_variant		1	NM_003010.4	P2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69539 AN: 151810 Hom.: 16802 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.458 AC: 69553 AN: 151928 Hom.: 16802 Cov.: 31 AF XY: 0.463 AC XY: 34360 AN XY: 74274

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.459

Alfa AF: 0.505 Hom.: 24239

Bravo AF: 0.447

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs10432016; hg19: chr17-11990679; COSMIC: COSV62255503;