rs2024144

Variant summary

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

The NM_015675.4(GADD45B):​c.369+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,433,700 control chromosomes in the GnomAD database, including 36,023 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 0.17 ( 2788 hom., cov: 32)
Exomes 𝑓: 0.22 ( 33235 hom. )

Consequence

GADD45B
NM_015675.4 intron

Scores

1
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02
Variant links:
Genes affected
GADD45B (HGNC:4096): (growth arrest and DNA damage inducible beta) This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The genes in this group respond to environmental stresses by mediating activation of the p38/JNK pathway. This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis. These genes are regulated by different mechanisms, but they are often coordinately expressed and can function cooperatively in inhibiting cell growth. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0020619333).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GADD45BNM_015675.4 linkuse as main transcriptc.369+28C>T intron_variant ENST00000215631.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GADD45BENST00000215631.9 linkuse as main transcriptc.369+28C>T intron_variant 1 NM_015675.4 P1
GADD45BENST00000587345.1 linkuse as main transcriptc.397C>T p.His133Tyr missense_variant 3/32
GADD45BENST00000592937.1 linkuse as main transcriptn.1027C>T non_coding_transcript_exon_variant 2/22
GADD45BENST00000585359.1 linkuse as main transcriptc.*184+28C>T intron_variant, NMD_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.168
AC:
25567
AN:
152052
Hom.:
2787
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0430
Gnomad AMI
AF:
0.282
Gnomad AMR
AF:
0.163
Gnomad ASJ
AF:
0.248
Gnomad EAS
AF:
0.433
Gnomad SAS
AF:
0.262
Gnomad FIN
AF:
0.178
Gnomad MID
AF:
0.180
Gnomad NFE
AF:
0.212
Gnomad OTH
AF:
0.162
GnomAD3 exomes
AF:
0.238
AC:
35811
AN:
150198
Hom.:
4651
AF XY:
0.244
AC XY:
19837
AN XY:
81212
show subpopulations
Gnomad AFR exome
AF:
0.0428
Gnomad AMR exome
AF:
0.202
Gnomad ASJ exome
AF:
0.252
Gnomad EAS exome
AF:
0.455
Gnomad SAS exome
AF:
0.273
Gnomad FIN exome
AF:
0.215
Gnomad NFE exome
AF:
0.230
Gnomad OTH exome
AF:
0.217
GnomAD4 exome
AF:
0.223
AC:
285462
AN:
1281530
Hom.:
33235
Cov.:
19
AF XY:
0.225
AC XY:
142700
AN XY:
635094
show subpopulations
Gnomad4 AFR exome
AF:
0.0349
Gnomad4 AMR exome
AF:
0.188
Gnomad4 ASJ exome
AF:
0.242
Gnomad4 EAS exome
AF:
0.433
Gnomad4 SAS exome
AF:
0.266
Gnomad4 FIN exome
AF:
0.180
Gnomad4 NFE exome
AF:
0.220
Gnomad4 OTH exome
AF:
0.217
GnomAD4 genome
AF:
0.168
AC:
25563
AN:
152170
Hom.:
2788
Cov.:
32
AF XY:
0.170
AC XY:
12626
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.0429
Gnomad4 AMR
AF:
0.163
Gnomad4 ASJ
AF:
0.248
Gnomad4 EAS
AF:
0.433
Gnomad4 SAS
AF:
0.262
Gnomad4 FIN
AF:
0.178
Gnomad4 NFE
AF:
0.212
Gnomad4 OTH
AF:
0.162
Alfa
AF:
0.178
Hom.:
640
Bravo
AF:
0.163
TwinsUK
AF:
0.222
AC:
824
ALSPAC
AF:
0.225
AC:
868
ESP6500AA
AF:
0.0464
AC:
201
ESP6500EA
AF:
0.235
AC:
1985
ExAC
AF:
0.197
AC:
23167
Asia WGS
AF:
0.288
AC:
998
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
13
DANN
Benign
0.76
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.30
T
MetaRNN
Benign
0.0021
T
MutationTaster
Benign
1.0
P;P
Sift4G
Uncertain
0.060
T
Vest4
0.26
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs2024144; hg19: chr19-2477277; COSMIC: COSV53126018; COSMIC: COSV53126018; API