dbSNP rs2024144: GADD45B:c.369+28C>T (chr19-2477279-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GADD45B	NM_015675.4 link	c.369+28C>T		intron_variant	Intron 3 of 3	ENST00000215631.9	NP_056490.2	O75293

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45B	ENST00000215631.9 link	c.369+28C>T		intron_variant	Intron 3 of 3	1	NM_015675.4	ENSP00000215631.3		O75293

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

GnomAD2 exomes

AF:

0.238

AC:

35811

AN:

150198

AF XY:

0.244

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 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

African (AFR)

AF:

0.0349

AC:

1033

AN:

29600

American (AMR)

AF:

0.188

AC:

6355

AN:

33744

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

5104

AN:

21126

East Asian (EAS)

AF:

0.433

AC:

16159

AN:

37288

South Asian (SAS)

AF:

0.266

AC:

19635

AN:

73772

European-Finnish (FIN)

AF:

0.180

AC:

6655

AN:

36926

Middle Eastern (MID)

AF:

0.187

AC:

947

AN:

5054

European-Non Finnish (NFE)

AF:

0.220

AC:

217789

AN:

989804

Other (OTH)

AF:

0.217

AC:

11785

AN:

54216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12078

24157

36235

48314

60392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7616

15232

22848

30464

38080

<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:

0.168

AC:

25563

AN:

152170

Hom.:

2788

Cov.:

AF XY:

0.170

AC XY:

12626

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0429

AC:

1783

AN:

41546

American (AMR)

AF:

0.163

AC:

2493

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

860

AN:

3472

East Asian (EAS)

AF:

0.433

AC:

2237

AN:

5166

South Asian (SAS)

AF:

0.262

AC:

1263

AN:

4822

European-Finnish (FIN)

AF:

0.178

AC:

1881

AN:

10596

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14395

AN:

67970

Other (OTH)

AF:

0.162

AC:

343

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1045

2090

3135

4180

5225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.192

Hom.:

1296

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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.76

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0021

PhyloP100

2.0

Sift4G

Uncertain

0.060

Vest4

0.26

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over