Genetic Variant GADD45B:c.369+67G>A (chr19-2477318-G-A) – 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+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,203,168 control chromosomes in the GnomAD database, including 163,310 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 0.47 ( 17471 hom., cov: 32)

Exomes 𝑓: 0.52 ( 145839 hom. )

Consequence

GADD45B
NM_015675.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.474

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=3.5640966E-5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45B	NM_015675.4 link	c.369+67G>A		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+67G>A		intron_variant	Intron 3 of 3	1	NM_015675.4	ENSP00000215631.3		O75293

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70902

AN:

151942

Hom.:

17445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.572

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.518

AC:

54918

AN:

105922

AF XY:

0.525

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.555

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.438

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.524

AC:

551013

AN:

1051108

Hom.:

145839

Cov.:

AF XY:

0.526

AC XY:

275795

AN XY:

524612

show subpopulations

Gnomad4 AFR exome

AF:

0.309

AC:

7649

AN:

24762

Gnomad4 AMR exome

AF:

0.552

AC:

15435

AN:

27946

Gnomad4 ASJ exome

AF:

0.563

AC:

10586

AN:

18816

Gnomad4 EAS exome

AF:

0.462

AC:

15913

AN:

34442

Gnomad4 SAS exome

AF:

0.564

AC:

36908

AN:

65400

Gnomad4 FIN exome

AF:

0.418

AC:

14286

AN:

34212

Gnomad4 NFE exome

AF:

0.532

AC:

423045

AN:

795138

Gnomad4 Remaining exome

AF:

0.532

AC:

24670

AN:

46354

Heterozygous variant carriers

14711

29422

44133

58844

73555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

11256

22512

33768

45024

56280

<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:

0.467

AC:

70968

AN:

152060

Hom.:

17471

Cov.:

AF XY:

0.463

AC XY:

34445

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.326

AC:

0.325511

AN:

0.325511

Gnomad4 AMR

AF:

0.573

AC:

0.572587

AN:

0.572587

Gnomad4 ASJ

AF:

0.558

AC:

0.55767

AN:

0.55767

Gnomad4 EAS

AF:

0.449

AC:

0.448589

AN:

0.448589

Gnomad4 SAS

AF:

0.567

AC:

0.567427

AN:

0.567427

Gnomad4 FIN

AF:

0.396

AC:

0.395841

AN:

0.395841

Gnomad4 NFE

AF:

0.526

AC:

0.526124

AN:

0.526124

Gnomad4 OTH

AF:

0.543

AC:

0.543046

AN:

0.543046

Heterozygous variant carriers

1923

3845

5768

7690

9613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.523

Hom.:

40962

Bravo

AF:

0.473

TwinsUK

AF:

0.527

AC:

1954

ALSPAC

AF:

0.532

AC:

2049

ExAC

AF:

0.421

AC:

43905

Asia WGS

AF:

0.550

AC:

1915

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.24

CADD

Benign

4.8

DANN

Benign

0.89

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.39

MetaRNN

Benign

0.000036

Vest4

0.11

GERP RS

-9.1

Mutation Taster

=99/1

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

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