rs12603036

Variant names:

• chr17-12040384-C-T
• rs12603036
• NM_003010.4:c.116-14505C>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.116-14505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 152,204 control chromosomes in the GnomAD database, including 670 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 0.084 (670 hom., cov: 33)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K4	NM_003010.4	c.116-14505C>T		intron_variant	Intron 1 of 10	ENST00000353533.10	NP_003001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K4	ENST00000353533.10	c.116-14505C>T		intron_variant	Intron 1 of 10	1	NM_003010.4	ENSP00000262445.5

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12791 AN: 152086 Hom.: 670 Cov.: 33

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0957

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0840 AC: 12786 AN: 152204 Hom.: 670 Cov.: 33 AF XY: 0.0860 AC XY: 6400 AN XY: 74426

African (AFR) AF: 0.0186 AC: 772 AN: 41542

American (AMR) AF: 0.0954 AC: 1459 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3468

East Asian (EAS) AF: 0.103 AC: 536 AN: 5184

South Asian (SAS) AF: 0.0940 AC: 453 AN: 4820

European-Finnish (FIN) AF: 0.136 AC: 1442 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7362 AN: 67998

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.102 Hom.: 1569

Bravo AF: 0.0777

Asia WGS AF: 0.0960 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-0.34
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: rs12603036; hg19: chr17-11943701;