rs17205284

Positions:

• chr2-101786476-C-T

Variant summary

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

The NM_001395002.1(MAP4K4):​c.124-4244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 152,010 control chromosomes in the GnomAD database, including 473 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 0.067 (473 hom., cov: 31)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.124-4244C>T		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.124-4244C>T		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10216 AN: 151904 Hom.: 472 Cov.: 31

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0672 AC: 10220 AN: 152010 Hom.: 473 Cov.: 31 AF XY: 0.0658 AC XY: 4885 AN XY: 74288

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.0977

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0807 Hom.: 88

Bravo AF: 0.0614

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.74

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: rs17205284; hg19: chr2-102402938;