NM_003010.4:c.115+6663T>G

Variant names:

• chr17-12027664-T-G
• rs8067785
• NM_003010.4:c.115+6663T>G

Variant summary

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

The NM_003010.4(MAP2K4):​c.115+6663T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 152,222 control chromosomes in the GnomAD database, including 946 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 0.096 (946 hom., cov: 32)
• Consequence: MAP2K4 NM_003010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K4	NM_003010.4	c.115+6663T>G		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.115+6663T>G		intron_variant	Intron 1 of 10	1	NM_003010.4	ENSP00000262445.5

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14629 AN: 152104 Hom.: 946 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.0961 AC: 14632 AN: 152222 Hom.: 946 Cov.: 32 AF XY: 0.0954 AC XY: 7096 AN XY: 74416

African (AFR) AF: 0.0256 AC: 1062 AN: 41564

American (AMR) AF: 0.0878 AC: 1342 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3468

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5184

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1714 AN: 10592

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9569 AN: 67994

Other (OTH) AF: 0.0916 AC: 193 AN: 2106

Alfa AF: 0.117 Hom.: 1034

Bravo AF: 0.0866

Asia WGS AF: 0.0610 AC: 210 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	4.5
DANN	Benign	0.68
PhyloP100		0.27
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: rs8067785; hg19: chr17-11930981;