rs12939944

Positions:

• chr17-12056502-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003010.4(MAP2K4):​c.218+1511C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,778 control chromosomes in the GnomAD database, including 16,882 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 0.46 (16882 hom., cov: 32)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K4	NM_003010.4	c.218+1511C>T		intron_variant		ENST00000353533.10	NP_003001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K4	ENST00000353533.10	c.218+1511C>T		intron_variant		1	NM_003010.4	ENSP00000262445	P2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69659 AN: 151662 Hom.: 16883 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.459 AC: 69673 AN: 151778 Hom.: 16882 Cov.: 32 AF XY: 0.464 AC XY: 34421 AN XY: 74182

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.461

Alfa AF: 0.486 Hom.: 2325

Bravo AF: 0.447

Asia WGS AF: 0.543 AC: 1885 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs12939944; hg19: chr17-11959819;