rs3771904

Positions:

• chr2-101869213-T-A

Variant summary

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

The NM_001395002.1(MAP4K4):​c.2464-409T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,740 control chromosomes in the GnomAD database, including 29,562 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 0.61 (29562 hom., cov: 31)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.2464-409T>A		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.2464-409T>A		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92039 AN: 151622 Hom.: 29507 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.607 AC: 92157 AN: 151740 Hom.: 29562 Cov.: 31 AF XY: 0.607 AC XY: 45003 AN XY: 74174

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.564

Alfa AF: 0.593 Hom.: 3415

Bravo AF: 0.613

Asia WGS AF: 0.470 AC: 1621 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.63

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: rs3771904; hg19: chr2-102485675; COSMIC: COSV56328208; COSMIC: COSV56328208;