NM_003010.4:c.219-334C>T

Variant names:

• chr17-12081022-C-T
• rs9907196
• NM_003010.4:c.219-334C>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.219-334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,204 control chromosomes in the GnomAD database, including 2,595 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 0.17 (2595 hom., cov: 32)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K4	NM_003010.4	MANE Select	c.219-334C>T		intron	N/A	NP_003001.1
	MAP2K4	NM_001281435.2		c.252-334C>T		intron	N/A	NP_001268364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K4	ENST00000353533.10	TSL:1 MANE Select	c.219-334C>T		intron	N/A	ENSP00000262445.5
	MAP2K4	ENST00000415385.7	TSL:2	c.252-334C>T		intron	N/A	ENSP00000410402.3
	MAP2K4	ENST00000538465.7	TSL:5	n.26-14553C>T		intron	N/A	ENSP00000467239.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26066 AN: 152086 Hom.: 2592 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.171 AC: 26068 AN: 152204 Hom.: 2595 Cov.: 32 AF XY: 0.172 AC XY: 12768 AN XY: 74424

African (AFR) AF: 0.0751 AC: 3119 AN: 41548

American (AMR) AF: 0.177 AC: 2701 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3464

East Asian (EAS) AF: 0.185 AC: 955 AN: 5174

South Asian (SAS) AF: 0.302 AC: 1456 AN: 4822

European-Finnish (FIN) AF: 0.133 AC: 1405 AN: 10582

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14807 AN: 68008

Other (OTH) AF: 0.197 AC: 417 AN: 2112

Alfa AF: 0.196 Hom.: 818

Bravo AF: 0.166

Asia WGS AF: 0.220 AC: 763 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.52
DANN	Benign	0.16
PhyloP100		-0.92
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: rs9907196; hg19: chr17-11984339; COSMIC: COSV62255963; COSMIC: COSV62255963;