rs8136867

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002745.5(MAPK1):​c.119+16818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,952 control chromosomes in the GnomAD database, including 23,400 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23400 hom., cov: 32)

Consequence

MAPK1
NM_002745.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0110

Publications

33 publications found
Variant links:
Genes affected
MAPK1 (HGNC:6871): (mitogen-activated protein kinase 1) This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014]
MAPK1 Gene-Disease associations (from GenCC):
  • Noonan syndrome 13
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAPK1NM_002745.5 linkc.119+16818C>T intron_variant Intron 1 of 8 ENST00000215832.11 NP_002736.3 P28482-1Q1HBJ4Q499G7
MAPK1NM_138957.3 linkc.119+16818C>T intron_variant Intron 1 of 7 NP_620407.1 P28482-1Q1HBJ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAPK1ENST00000215832.11 linkc.119+16818C>T intron_variant Intron 1 of 8 1 NM_002745.5 ENSP00000215832.7 P28482-1
MAPK1ENST00000398822.7 linkc.119+16818C>T intron_variant Intron 1 of 7 1 ENSP00000381803.3 P28482-1
MAPK1ENST00000544786.1 linkc.119+16818C>T intron_variant Intron 1 of 6 1 ENSP00000440842.1 P28482-2

Frequencies

GnomAD3 genomes
AF:
0.552
AC:
83742
AN:
151834
Hom.:
23365
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.606
Gnomad AMI
AF:
0.541
Gnomad AMR
AF:
0.623
Gnomad ASJ
AF:
0.624
Gnomad EAS
AF:
0.448
Gnomad SAS
AF:
0.471
Gnomad FIN
AF:
0.378
Gnomad MID
AF:
0.627
Gnomad NFE
AF:
0.538
Gnomad OTH
AF:
0.595
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.552
AC:
83832
AN:
151952
Hom.:
23400
Cov.:
32
AF XY:
0.545
AC XY:
40506
AN XY:
74262
show subpopulations
African (AFR)
AF:
0.607
AC:
25144
AN:
41436
American (AMR)
AF:
0.623
AC:
9508
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.624
AC:
2168
AN:
3472
East Asian (EAS)
AF:
0.447
AC:
2311
AN:
5168
South Asian (SAS)
AF:
0.471
AC:
2273
AN:
4826
European-Finnish (FIN)
AF:
0.378
AC:
3969
AN:
10508
Middle Eastern (MID)
AF:
0.644
AC:
188
AN:
292
European-Non Finnish (NFE)
AF:
0.538
AC:
36531
AN:
67964
Other (OTH)
AF:
0.591
AC:
1250
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1958
3916
5874
7832
9790
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
716
1432
2148
2864
3580
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.545
Hom.:
86433
Bravo
AF:
0.570
Asia WGS
AF:
0.475
AC:
1650
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
3.8
DANN
Benign
0.48
PhyloP100
0.011
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs8136867; hg19: chr22-22204793; API