Variant 2-101698595-A-G 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.123+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,519,914 control chromosomes in the GnomAD database, including 64,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5491 hom., cov: 31)

Exomes 𝑓: 0.29 ( 59443 hom. )

Consequence

MAP4K4
NM_001395002.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.528

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=-0.81).

BP6

Variant 2-101698595-A-G is Benign according to our data. Variant chr2-101698595-A-G is described in ClinVar as [Benign]. Clinvar id is 1243012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 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.123+57A>G		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9 linkuse as main transcript	c.123+57A>G		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37393

AN:

151470

Hom.:

5490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0971

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.288

AC:

394055

AN:

1368326

Hom.:

59443

AF XY:

0.285

AC XY:

195308

AN XY:

685896

show subpopulations

Gnomad4 AFR exome

AF:

0.0887

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.247

AC:

37405

AN:

151588

Hom.:

5491

Cov.:

AF XY:

0.252

AC XY:

18615

AN XY:

74016

show subpopulations

Gnomad4 AFR

AF:

0.0970

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.225

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.309

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.278

Hom.:

6766

Bravo

AF:

0.232

Asia WGS

AF:

0.180

AC:

630

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 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

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

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