2-101827359-C-G

Variant names:

• chr2-101827359-C-G
• rs2236936
• NM_001395002.1:c.417+1930C>G

Variant summary

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

The NM_001395002.1(MAP4K4):​c.417+1930C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,046 control chromosomes in the GnomAD database, including 43,579 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 0.75 (43579 hom., cov: 31)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

Genes affected

MAP4K4 (HGNC:6866): (mitogen-activated protein kinase kinase kinase kinase 4) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4K4	NM_001395002.1	c.417+1930C>G		intron_variant	Intron 5 of 32	ENST00000324219.9	NP_001381931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4K4	ENST00000324219.9	c.417+1930C>G		intron_variant	Intron 5 of 32	5	NM_001395002.1	ENSP00000313644.6

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114399 AN: 151928 Hom.: 43523 Cov.: 31

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.753 AC: 114510 AN: 152046 Hom.: 43579 Cov.: 31 AF XY: 0.755 AC XY: 56109 AN XY: 74304

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.729

Alfa AF: 0.635 Hom.: 1774

Bravo AF: 0.756

Asia WGS AF: 0.787 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.58

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: rs2236936; hg19: chr2-102443821;