chr15-66491272-G-A

Variant summary

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

The NM_002755.4(MAP2K1):​c.*657G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 237,318 control chromosomes in the GnomAD database, including 586 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 0.056 ( 343 hom., cov: 32)
Exomes 𝑓: 0.067 ( 243 hom. )

Consequence

MAP2K1
NM_002755.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.848

Publications

12 publications found
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]
SNAPC5 (HGNC:15484): (small nuclear RNA activating complex polypeptide 5) This gene encodes a subunit of the small nuclear RNA (snRNA)-activating protein complex that plays a role in the transcription of snRNA genes. This complex binds to the promoters of snRNA genes transcribed by either RNA polymerase II or III and recruits other regulatory factors to activate snRNA gene transcription. The encoded protein may play a role in stabilizing this complex. A pseudogene of this gene has been identified on chromosome 6. [provided by RefSeq, Jul 2016]

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=-0.58).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP2K1NM_002755.4 linkc.*657G>A 3_prime_UTR_variant Exon 11 of 11 ENST00000307102.10 NP_002746.1 Q02750-1A4QPA9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP2K1ENST00000307102.10 linkc.*657G>A 3_prime_UTR_variant Exon 11 of 11 1 NM_002755.4 ENSP00000302486.5 Q02750-1

Frequencies

GnomAD3 genomes
AF:
0.0563
AC:
8556
AN:
152052
Hom.:
342
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0222
Gnomad AMI
AF:
0.0901
Gnomad AMR
AF:
0.0443
Gnomad ASJ
AF:
0.0931
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0286
Gnomad FIN
AF:
0.0802
Gnomad MID
AF:
0.114
Gnomad NFE
AF:
0.0793
Gnomad OTH
AF:
0.0652
GnomAD4 exome
AF:
0.0665
AC:
5665
AN:
85148
Hom.:
243
Cov.:
0
AF XY:
0.0671
AC XY:
2654
AN XY:
39574
show subpopulations
African (AFR)
AF:
0.0206
AC:
80
AN:
3878
American (AMR)
AF:
0.0391
AC:
138
AN:
3532
Ashkenazi Jewish (ASJ)
AF:
0.103
AC:
524
AN:
5110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
11314
South Asian (SAS)
AF:
0.0229
AC:
28
AN:
1222
European-Finnish (FIN)
AF:
0.0785
AC:
41
AN:
522
Middle Eastern (MID)
AF:
0.102
AC:
50
AN:
492
European-Non Finnish (NFE)
AF:
0.0818
AC:
4269
AN:
52170
Other (OTH)
AF:
0.0774
AC:
535
AN:
6908
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
251
503
754
1006
1257
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0562
AC:
8556
AN:
152170
Hom.:
343
Cov.:
32
AF XY:
0.0561
AC XY:
4172
AN XY:
74402
show subpopulations
African (AFR)
AF:
0.0222
AC:
921
AN:
41502
American (AMR)
AF:
0.0442
AC:
676
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.0931
AC:
323
AN:
3470
East Asian (EAS)
AF:
0.000579
AC:
3
AN:
5182
South Asian (SAS)
AF:
0.0293
AC:
141
AN:
4818
European-Finnish (FIN)
AF:
0.0802
AC:
849
AN:
10586
Middle Eastern (MID)
AF:
0.109
AC:
32
AN:
294
European-Non Finnish (NFE)
AF:
0.0793
AC:
5393
AN:
68010
Other (OTH)
AF:
0.0645
AC:
136
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
393
787
1180
1574
1967
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
98
196
294
392
490
<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:
0.0754
Hom.:
565
Bravo
AF:
0.0521
Asia WGS
AF:
0.0210
AC:
73
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.94
DANN
Benign
0.51
PhyloP100
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=98/2
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: rs8684; hg19: chr15-66783610; API