rs2322123

Variant names:

• chr17-12050190-G-A
• rs2322123
• NM_003010.4:c.116-4699G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_003010.4(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 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003010.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K4	NM_003010.4	MANE Select	c.116-4699G>A		intron	N/A	NP_003001.1	P45985-1
	MAP2K4	NM_001281435.2		c.149-4699G>A		intron	N/A	NP_001268364.1	P45985-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K4	ENST00000353533.10	TSL:1 MANE Select	c.116-4699G>A		intron	N/A	ENSP00000262445.5	P45985-1
	MAP2K4	ENST00000415385.7	TSL:2	c.149-4699G>A		intron	N/A	ENSP00000410402.3	P45985-2
	MAP2K4	ENST00000905332.1		c.116-4753G>A		intron	N/A	ENSP00000575391.1

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

African (AFR) AF: 0.456 AC: 18877 AN: 41390

American (AMR) AF: 0.714 AC: 10913 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2769 AN: 3466

East Asian (EAS) AF: 0.813 AC: 4195 AN: 5160

South Asian (SAS) AF: 0.803 AC: 3875 AN: 4826

European-Finnish (FIN) AF: 0.717 AC: 7549 AN: 10530

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50675 AN: 67972

Other (OTH) AF: 0.689 AC: 1458 AN: 2116

Alfa AF: 0.721 Hom.: 51131

Bravo AF: 0.652

Asia WGS AF: 0.794 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.2
DANN	Benign	0.38
PhyloP100		0.87
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: rs2322123; hg19: chr17-11953507;