17-12077761-C-T

Variant names:

• chr17-12077761-C-T
• rs11653406
• NM_003010.4:c.219-3595C>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.219-3595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,036 control chromosomes in the GnomAD database, including 17,694 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 0.47 (17694 hom., cov: 32)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K4	NM_003010.4	c.219-3595C>T		intron_variant	Intron 2 of 10	ENST00000353533.10	NP_003001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K4	ENST00000353533.10	c.219-3595C>T		intron_variant	Intron 2 of 10	1	NM_003010.4	ENSP00000262445.5

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71622 AN: 151918 Hom.: 17693 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.471 AC: 71639 AN: 152036 Hom.: 17694 Cov.: 32 AF XY: 0.476 AC XY: 35395 AN XY: 74308

African (AFR) AF: 0.308 AC: 12786 AN: 41476

American (AMR) AF: 0.531 AC: 8101 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3466

East Asian (EAS) AF: 0.610 AC: 3149 AN: 5160

South Asian (SAS) AF: 0.500 AC: 2408 AN: 4812

European-Finnish (FIN) AF: 0.582 AC: 6146 AN: 10552

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35692 AN: 67986

Other (OTH) AF: 0.475 AC: 1002 AN: 2110

Alfa AF: 0.495 Hom.: 4382

Bravo AF: 0.462

Asia WGS AF: 0.555 AC: 1931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.14
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: rs11653406; hg19: chr17-11981078;