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GeneBe

19-7911099-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_145185.4(MAP2K7):c.795C>T(p.Ser265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,612,396 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MAP2K7
NM_145185.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.638
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-7911099-C-T is Benign according to our data. Variant chr19-7911099-C-T is described in ClinVar as [Benign]. Clinvar id is 734209.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.638 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 45 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP2K7NM_145185.4 linkuse as main transcriptc.795C>T p.Ser265= synonymous_variant 7/11 ENST00000397979.4
MAP2K7NM_001297555.2 linkuse as main transcriptc.843C>T p.Ser281= synonymous_variant 8/12
MAP2K7NM_001297556.2 linkuse as main transcriptc.795C>T p.Ser265= synonymous_variant 7/11
MAP2K7XM_006722800.3 linkuse as main transcriptc.843C>T p.Ser281= synonymous_variant 8/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP2K7ENST00000397979.4 linkuse as main transcriptc.795C>T p.Ser265= synonymous_variant 7/111 NM_145185.4 P4O14733-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000296
AC:
45
AN:
152062
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00463
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000347
AC:
85
AN:
245184
Hom.:
0
AF XY:
0.000343
AC XY:
46
AN XY:
134176
show subpopulations
Gnomad AFR exome
AF:
0.0000663
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00369
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000109
Gnomad OTH exome
AF:
0.000335
GnomAD4 exome
AF:
0.000207
AC:
302
AN:
1460216
Hom.:
0
Cov.:
35
AF XY:
0.000195
AC XY:
142
AN XY:
726416
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00214
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000155
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000296
AC:
45
AN:
152180
Hom.:
2
Cov.:
33
AF XY:
0.000309
AC XY:
23
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00464
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000131
Hom.:
0
Bravo
AF:
0.000261
Asia WGS
AF:
0.00404
AC:
14
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 submitterclinical testingInvitaeAug 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
7.0
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs372642511; hg19: chr19-7975984; API