Variant rs2024144 details in Genebe, Genetics Data Aggregator

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

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]

GADD45B links:

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
GADD45B	NM_015675.4 linkuse as main transcript	c.369+28C>T		intron_variant		ENST00000215631.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GADD45B	ENST00000215631.9 linkuse as main transcript	c.369+28C>T		intron_variant		1	NM_015675.4	P1
GADD45B	ENST00000587345.1 linkuse as main transcript	c.397C>T	p.His133Tyr	missense_variant	3/3	2
GADD45B	ENST00000592937.1 linkuse as main transcript	n.1027C>T		non_coding_transcript_exon_variant	2/2	2
GADD45B	ENST00000585359.1 linkuse as main transcript	c.*184+28C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25567

AN:

152052

Hom.:

2787

Cov.:

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.:

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.:

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

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.76

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0021

MutationTaster

Benign

1.0

P;P

Sift4G

Uncertain

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over