rs252902

Variant summary

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

The NM_005921.2(MAP3K1):​c.482+4203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 176,670 control chromosomes in the GnomAD database, including 53,408 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 0.77 ( 45375 hom., cov: 31)
Exomes 𝑓: 0.81 ( 8033 hom. )

Consequence

MAP3K1
NM_005921.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660
Variant links:
Genes affected
MAP3K1 (HGNC:6848): (mitogen-activated protein kinase kinase kinase 1) The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]

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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=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP3K1NM_005921.2 linkuse as main transcriptc.482+4203A>G intron_variant ENST00000399503.4
MAP3K1XM_047417219.1 linkuse as main transcriptc.-488A>G 5_prime_UTR_variant 2/21
MAP3K1XM_047417218.1 linkuse as main transcriptc.482+4203A>G intron_variant
MAP3K1XM_047417220.1 linkuse as main transcriptc.-20-468A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP3K1ENST00000399503.4 linkuse as main transcriptc.482+4203A>G intron_variant 1 NM_005921.2 P1

Frequencies

GnomAD3 genomes
AF:
0.770
AC:
116864
AN:
151828
Hom.:
45323
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.733
Gnomad AMI
AF:
0.711
Gnomad AMR
AF:
0.675
Gnomad ASJ
AF:
0.817
Gnomad EAS
AF:
0.579
Gnomad SAS
AF:
0.771
Gnomad FIN
AF:
0.808
Gnomad MID
AF:
0.710
Gnomad NFE
AF:
0.820
Gnomad OTH
AF:
0.767
GnomAD4 exome
AF:
0.806
AC:
19922
AN:
24724
Hom.:
8033
AF XY:
0.806
AC XY:
9645
AN XY:
11964
show subpopulations
Gnomad4 AFR exome
AF:
0.677
Gnomad4 AMR exome
AF:
0.700
Gnomad4 ASJ exome
AF:
0.796
Gnomad4 EAS exome
AF:
0.670
Gnomad4 SAS exome
AF:
0.729
Gnomad4 FIN exome
AF:
0.500
Gnomad4 NFE exome
AF:
0.812
Gnomad4 OTH exome
AF:
0.759
GnomAD4 genome
AF:
0.770
AC:
116970
AN:
151946
Hom.:
45375
Cov.:
31
AF XY:
0.765
AC XY:
56828
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.733
Gnomad4 AMR
AF:
0.675
Gnomad4 ASJ
AF:
0.817
Gnomad4 EAS
AF:
0.581
Gnomad4 SAS
AF:
0.771
Gnomad4 FIN
AF:
0.808
Gnomad4 NFE
AF:
0.820
Gnomad4 OTH
AF:
0.769
Alfa
AF:
0.762
Hom.:
11354
Bravo
AF:
0.755
Asia WGS
AF:
0.698
AC:
2424
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
3.4
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs252902; hg19: chr5-56116085; API