Variant 6-90518704-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_145331.3(MAP3K7):c.1525-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 595,778 control chromosomes in the GnomAD database, including 19,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4640 hom., cov: 32)

Exomes 𝑓: 0.25 ( 15005 hom. )

Consequence

MAP3K7
NM_145331.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

MAP3K7 (HGNC:6859): (mitogen-activated protein kinase kinase kinase 7) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MAP3K7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 6-90518704-A-G is Benign according to our data. Variant chr6-90518704-A-G is described in ClinVar as [Benign]. Clinvar id is 1276654.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K7	NM_145331.3 linkuse as main transcript	c.1525-142T>C		intron_variant		ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8 linkuse as main transcript	c.1525-142T>C		intron_variant		1	NM_145331.3	ENSP00000358335	P3	O43318-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36326

AN:

151608

Hom.:

4642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.0983

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.235

GnomAD4 exome

AF:

0.248

AC:

109967

AN:

444052

Hom.:

15005

AF XY:

0.242

AC XY:

58191

AN XY:

240450

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.0873

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.239

AC:

36319

AN:

151726

Hom.:

4640

Cov.:

AF XY:

0.238

AC XY:

17649

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.243

Gnomad4 EAS

AF:

0.0987

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.270

Hom.:

716

Bravo

AF:

0.227

Asia WGS

AF:

0.157

AC:

544

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.82

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