Variant rs1139583 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001395002.1(MAP4K4):c.1254A>G(p.Glu418Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,549,936 control chromosomes in the GnomAD database, including 21,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1722 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19460 hom. )

Consequence

MAP4K4
NM_001395002.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.807

Variant links:

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 links:

MAP4K4 (HGNC:):

MAP4K4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-101855997-A-G is Benign according to our data. Variant chr2-101855997-A-G is described in ClinVar as [Benign]. Clinvar id is 1183614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.807 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K4	NM_001395002.1 linkuse as main transcript	c.1254A>G	p.Glu418Glu	synonymous_variant	13/33	ENST00000324219.9	NP_001381931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K4	ENST00000324219.9 linkuse as main transcript	c.1254A>G	p.Glu418Glu	synonymous_variant	13/33	5	NM_001395002.1	ENSP00000313644.6		G5E948

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22146

AN:

152062

Hom.:

1721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.0820

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.150

AC:

22990

AN:

153544

Hom.:

1888

AF XY:

0.157

AC XY:

12747

AN XY:

81408

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.0859

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.0727

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.164

AC:

228656

AN:

1397756

Hom.:

19460

Cov.:

AF XY:

0.166

AC XY:

114205

AN XY:

689492

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.0908

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.198

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.146

AC:

22147

AN:

152180

Hom.:

1722

Cov.:

AF XY:

0.146

AC XY:

10881

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.0814

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.163

Hom.:

5418

Bravo

AF:

0.139

Asia WGS

AF:

0.189

AC:

654

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over