rs17614045

Variant names:

• chr17-12047137-C-G
• rs17614045
• NM_003010.4:c.116-7752C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-12047137-C-G
• chr17-12047137-C-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.116-7752C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,558 control chromosomes in the GnomAD database, including 5,176 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 0.24 (5176 hom., cov: 31)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.116-7752C>G		intron	N/A	NP_003001.1	P45985-1
	MAP2K4	NM_001281435.2		c.149-7752C>G		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.116-7752C>G		intron	N/A	ENSP00000262445.5	P45985-1
	MAP2K4	ENST00000415385.7	TSL:2	c.149-7752C>G		intron	N/A	ENSP00000410402.3	P45985-2
	MAP2K4	ENST00000905332.1		c.116-7806C>G		intron	N/A	ENSP00000575391.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36813 AN: 151438 Hom.: 5176 Cov.: 31

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.355

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.243 AC: 36800 AN: 151558 Hom.: 5176 Cov.: 31 AF XY: 0.243 AC XY: 17961 AN XY: 74044

African (AFR) AF: 0.0870 AC: 3593 AN: 41304

American (AMR) AF: 0.247 AC: 3757 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1229 AN: 3466

East Asian (EAS) AF: 0.184 AC: 950 AN: 5160

South Asian (SAS) AF: 0.311 AC: 1493 AN: 4796

European-Finnish (FIN) AF: 0.280 AC: 2914 AN: 10420

Middle Eastern (MID) AF: 0.347 AC: 100 AN: 288

European-Non Finnish (NFE) AF: 0.323 AC: 21926 AN: 67890

Other (OTH) AF: 0.285 AC: 599 AN: 2100

Alfa AF: 0.161 Hom.: 330

Bravo AF: 0.230

Asia WGS AF: 0.221 AC: 765 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-2.7
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: rs17614045; hg19: chr17-11950454; COSMIC: COSV62255816;