Variant chr2-101698156-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001395002.1(MAP4K4):c.57+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,165,182 control chromosomes in the GnomAD database, including 921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 59 hom., cov: 32)

Exomes 𝑓: 0.038 ( 862 hom. )

Consequence

MAP4K4
NM_001395002.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.261

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-101698156-G-A is Benign according to our data. Variant chr2-101698156-G-A is described in ClinVar as [Benign]. Clinvar id is 1183785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1 linkuse as main transcript	c.57+19G>A		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9 linkuse as main transcript	c.57+19G>A		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

3693

AN:

140444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00651

Gnomad AMI

AF:

0.0930

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0556

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.0433

Gnomad NFE

AF:

0.0383

Gnomad OTH

AF:

0.0231

GnomAD3 exomes

AF:

0.0325

AC:

5625

AN:

173206

Hom.:

117

AF XY:

0.0353

AC XY:

3474

AN XY:

98428

show subpopulations

Gnomad AFR exome

AF:

0.00545

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0431

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0578

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0374

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0377

AC:

38662

AN:

1024636

Hom.:

862

Cov.:

AF XY:

0.0389

AC XY:

19493

AN XY:

500870

show subpopulations

Gnomad4 AFR exome

AF:

0.00535

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.000106

Gnomad4 SAS exome

AF:

0.0624

Gnomad4 FIN exome

AF:

0.0235

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0398

GnomAD4 genome

AF:

0.0263

AC:

3692

AN:

140546

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1785

AN XY:

68352

show subpopulations

Gnomad4 AFR

AF:

0.00649

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0560

Gnomad4 FIN

AF:

0.0202

Gnomad4 NFE

AF:

0.0383

Gnomad4 OTH

AF:

0.0228

Alfa

AF:

0.0325

Hom.:

Bravo

AF:

0.0234

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	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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