17-12038166-C-T

Variant names:

• chr17-12038166-C-T
• rs7216812
• NM_003010.4:c.116-16723C>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.116-16723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,890 control chromosomes in the GnomAD database, including 12,133 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 0.39 (12133 hom., cov: 32)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K4	NM_003010.4	c.116-16723C>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.116-16723C>T		intron_variant	Intron 1 of 10	1	NM_003010.4	ENSP00000262445.5

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59547 AN: 151770 Hom.: 12128 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.392 AC: 59570 AN: 151890 Hom.: 12133 Cov.: 32 AF XY: 0.398 AC XY: 29556 AN XY: 74224

African (AFR) AF: 0.275 AC: 11411 AN: 41438

American (AMR) AF: 0.457 AC: 6971 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3472

East Asian (EAS) AF: 0.580 AC: 2996 AN: 5162

South Asian (SAS) AF: 0.497 AC: 2392 AN: 4814

European-Finnish (FIN) AF: 0.439 AC: 4625 AN: 10536

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28398 AN: 67882

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.413 Hom.: 40634

Bravo AF: 0.388

Asia WGS AF: 0.539 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.68
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: rs7216812; hg19: chr17-11941483;