chr6-161047785-A-G

Variant names:

• chr6-161047785-A-G
• rs1822520
• NM_005922.4:c.344-831A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005922.4(MAP3K4):​c.344-831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,132 control chromosomes in the GnomAD database, including 37,296 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 0.69 (37296 hom., cov: 32)
• Consequence: MAP3K4 NM_005922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

MAP3K4 (HGNC:6856): (mitogen-activated protein kinase kinase kinase 4) The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K4	NM_005922.4	c.344-831A>G		intron_variant	Intron 2 of 26	ENST00000392142.9	NP_005913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K4	ENST00000392142.9	c.344-831A>G		intron_variant	Intron 2 of 26	1	NM_005922.4	ENSP00000375986.4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104212 AN: 152014 Hom.: 37291 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.685 AC: 104246 AN: 152132 Hom.: 37296 Cov.: 32 AF XY: 0.690 AC XY: 51325 AN XY: 74346

African (AFR) AF: 0.468 AC: 19414 AN: 41500

American (AMR) AF: 0.784 AC: 11990 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2840 AN: 3468

East Asian (EAS) AF: 0.969 AC: 5021 AN: 5182

South Asian (SAS) AF: 0.826 AC: 3990 AN: 4828

European-Finnish (FIN) AF: 0.710 AC: 7490 AN: 10552

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51091 AN: 67992

Other (OTH) AF: 0.698 AC: 1474 AN: 2112

Alfa AF: 0.741 Hom.: 70287

Bravo AF: 0.683

Asia WGS AF: 0.847 AC: 2946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.043
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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs1822520; hg19: chr6-161468817;