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GeneBe

19-7910773-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_145185.4(MAP2K7):c.645C>T(p.Pro215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,610,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P215P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

MAP2K7
NM_145185.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.80
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 -11 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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-7910773-C-T is Benign according to our data. Variant chr19-7910773-C-T is described in ClinVar as [Benign]. Clinvar id is 717082.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=-3.8 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 228 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP2K7NM_145185.4 linkuse as main transcriptc.645C>T p.Pro215= synonymous_variant 6/11 ENST00000397979.4
MAP2K7NM_001297555.2 linkuse as main transcriptc.693C>T p.Pro231= synonymous_variant 7/12
MAP2K7NM_001297556.2 linkuse as main transcriptc.645C>T p.Pro215= synonymous_variant 6/11
MAP2K7XM_006722800.3 linkuse as main transcriptc.693C>T p.Pro231= synonymous_variant 7/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP2K7ENST00000397979.4 linkuse as main transcriptc.645C>T p.Pro215= synonymous_variant 6/111 NM_145185.4 P4O14733-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00150
AC:
228
AN:
151718
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00339
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000804
AC:
194
AN:
241312
Hom.:
1
AF XY:
0.000718
AC XY:
95
AN XY:
132280
show subpopulations
Gnomad AFR exome
AF:
0.00328
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000170
Gnomad SAS exome
AF:
0.000232
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000406
Gnomad OTH exome
AF:
0.00203
GnomAD4 exome
AF:
0.000503
AC:
733
AN:
1458294
Hom.:
1
Cov.:
35
AF XY:
0.000500
AC XY:
363
AN XY:
725422
show subpopulations
Gnomad4 AFR exome
AF:
0.00294
Gnomad4 AMR exome
AF:
0.00249
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000309
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000380
Gnomad4 OTH exome
AF:
0.000963
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00150
AC:
228
AN:
151830
Hom.:
0
Cov.:
33
AF XY:
0.00147
AC XY:
109
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.00338
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000632
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.0000660
Hom.:
3
Bravo
AF:
0.00193

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 testingInvitaeJan 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
0.43
Dann
Benign
0.74

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: rs117765980; hg19: chr19-7975658; COSMIC: COSV67607601; COSMIC: COSV67607601; API