Variant 19-7911242-C-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_145185.4(MAP2K7):c.856-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,610,038 control chromosomes in the GnomAD database, including 9,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 777 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9004 hom. )

Consequence

MAP2K7
NM_145185.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003761

Clinical Significance

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

Conservation

PhyloP100: -2.62

Variant links:

Genes affected

MAP2K7 (HGNC:6847): (mitogen-activated protein kinase kinase 7) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2,MAP3K3/MEKK5, and MAP4K2/GCK. This kinase is involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MAP2K7 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=-0.87).

BP6

Variant 19-7911242-C-G is Benign according to our data. Variant chr19-7911242-C-G is described in ClinVar as [Benign]. Clinvar id is 1222270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MAP2K7	NM_145185.4 linkuse as main transcript	c.856-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000397979.4	NP_660186.1
MAP2K7	NM_001297555.2 linkuse as main transcript	c.904-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001284484.1
MAP2K7	NM_001297556.2 linkuse as main transcript	c.856-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001284485.1
MAP2K7	XM_006722800.3 linkuse as main transcript	c.904-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_006722863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K7	ENST00000397979.4 linkuse as main transcript	c.856-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145185.4	ENSP00000381066	P4	O14733-1

Frequencies

GnomAD3 genomes

AF:

0.0886

AC:

13451

AN:

151788

Hom.:

775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0950

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.117

AC:

28665

AN:

245342

Hom.:

1953

AF XY:

0.115

AC XY:

15377

AN XY:

133996

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0999

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.105

AC:

153122

AN:

1458132

Hom.:

9004

Cov.:

AF XY:

0.105

AC XY:

76366

AN XY:

725428

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.246

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0986

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0886

AC:

13466

AN:

151906

Hom.:

777

Cov.:

AF XY:

0.0905

AC XY:

6722

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0353

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0950

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0251

Hom.:

Bravo

AF:

0.0896

EpiCase

AF:

0.101

EpiControl

AF:

0.100

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 28, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.040

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.036

SpliceAI score (max)

0.090

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