15-66468004-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002755.4(MAP2K1):​c.569-13751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,248 control chromosomes in the GnomAD database, including 3,448 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 0.21 ( 3448 hom., cov: 33)

Consequence

MAP2K1
NM_002755.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.198
Variant links:
Genes affected
MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

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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=-0.64).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAP2K1NM_002755.4 linkuse as main transcriptc.569-13751A>G intron_variant ENST00000307102.10 NP_002746.1 Q02750-1A4QPA9
MAP2K1NM_001411065.1 linkuse as main transcriptc.425-13751A>G intron_variant NP_001397994.1
MAP2K1XM_011521783.4 linkuse as main transcriptc.503-13751A>G intron_variant XP_011520085.1 B4DFY5
MAP2K1XM_017022411.3 linkuse as main transcriptc.491-13751A>G intron_variant XP_016877900.1 Q02750-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAP2K1ENST00000307102.10 linkuse as main transcriptc.569-13751A>G intron_variant 1 NM_002755.4 ENSP00000302486.5 Q02750-1

Frequencies

GnomAD3 genomes
AF:
0.210
AC:
31938
AN:
152130
Hom.:
3443
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.234
Gnomad AMI
AF:
0.226
Gnomad AMR
AF:
0.216
Gnomad ASJ
AF:
0.236
Gnomad EAS
AF:
0.378
Gnomad SAS
AF:
0.198
Gnomad FIN
AF:
0.204
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.181
Gnomad OTH
AF:
0.216
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.210
AC:
31964
AN:
152248
Hom.:
3448
Cov.:
33
AF XY:
0.211
AC XY:
15678
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.235
Gnomad4 AMR
AF:
0.215
Gnomad4 ASJ
AF:
0.236
Gnomad4 EAS
AF:
0.378
Gnomad4 SAS
AF:
0.197
Gnomad4 FIN
AF:
0.204
Gnomad4 NFE
AF:
0.181
Gnomad4 OTH
AF:
0.215
Alfa
AF:
0.180
Hom.:
2919
Bravo
AF:
0.216
Asia WGS
AF:
0.268
AC:
928
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
14
DANN
Benign
0.96

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: rs8039880; hg19: chr15-66760342; API