rs2322123

Positions:

• chr17-12050190-G-A
• chr17-12050190-G-C
• chr17-12050190-G-T

Variant summary

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

The ENST00000353533.10(MAP2K4):​c.116-4699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,940 control chromosomes in the GnomAD database, including 35,019 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 (35019 hom., cov: 30)
• Consequence: MAP2K4 ENST00000353533.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K4	NM_003010.4	c.116-4699G>A		intron_variant		ENST00000353533.10	NP_003001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K4	ENST00000353533.10	c.116-4699G>A		intron_variant		1	NM_003010.4	ENSP00000262445	P2

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101044 AN: 151824 Hom.: 35009 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.665 AC: 101096 AN: 151940 Hom.: 35019 Cov.: 30 AF XY: 0.670 AC XY: 49721 AN XY: 74254

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.689

Alfa AF: 0.733 Hom.: 39960

Bravo AF: 0.652

Asia WGS AF: 0.794 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.2
DANN	Benign	0.38

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: rs2322123; hg19: chr17-11953507;