2-101766631-A-T

Position:

• chr2-101766631-A-T

Variant summary

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

The NM_001395002.1(MAP4K4):​c.124-24089A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 150,606 control chromosomes in the GnomAD database, including 23,646 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 0.53 (23646 hom., cov: 29)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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]

MAP4K4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K4	NM_001395002.1	c.124-24089A>T		intron_variant		ENST00000324219.9	NP_001381931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K4	ENST00000324219.9	c.124-24089A>T		intron_variant		5	NM_001395002.1	ENSP00000313644.6

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80058 AN: 150506 Hom.: 23644 Cov.: 29

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.532 AC: 80060 AN: 150606 Hom.: 23646 Cov.: 29 AF XY: 0.540 AC XY: 39731 AN XY: 73602

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.553

Alfa AF: 0.574 Hom.: 3246

Bravo AF: 0.504

Asia WGS AF: 0.678 AC: 2352 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.67

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: rs13003883; hg19: chr2-102383093;