dbSNP rs3783469: GADD45A:c.384+116T>C (chr1-67686703-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001924.4(GADD45A):c.384+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 840,512 control chromosomes in the GnomAD database, including 2,067 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 0.068 ( 359 hom., cov: 34)

Exomes 𝑓: 0.067 ( 1708 hom. )

Consequence

GADD45A
NM_001924.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.539

Publications

1 publications found

Variant links:

Genes affected

GADD45A (HGNC:4095): (growth arrest and DNA damage inducible alpha) 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 protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Dec 2010]

GADD45A links:

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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4 link	c.384+116T>C	intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1	P24522-1
GADD45A	NM_001199741.2 link	c.282+116T>C	intron_variant	Intron 2 of 2		NP_001186670.1	P24522-2
GADD45A	NM_001199742.2 link	c.146+577T>C	intron_variant	Intron 2 of 2		NP_001186671.1	P24522A5JUZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9 link	c.384+116T>C		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4		P24522-1

Frequencies

GnomAD3 genomes

AF:

0.0679

AC:

10342

AN:

152202

Hom.:

361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.0606

Gnomad SAS

AF:

0.0755

Gnomad FIN

AF:

0.0655

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0762

Gnomad OTH

AF:

0.0635

GnomAD4 exome

AF:

0.0669

AC:

46011

AN:

688192

Hom.:

1708

AF XY:

0.0666

AC XY:

23444

AN XY:

351840

show subpopulations

African (AFR)

AF:

0.0659

AC:

1112

AN:

16876

American (AMR)

AF:

0.0388

AC:

798

AN:

20564

Ashkenazi Jewish (ASJ)

AF:

0.0355

AC:

545

AN:

15372

East Asian (EAS)

AF:

0.0360

AC:

1159

AN:

32226

South Asian (SAS)

AF:

0.0670

AC:

3498

AN:

52228

European-Finnish (FIN)

AF:

0.0635

AC:

2166

AN:

34120

Middle Eastern (MID)

AF:

0.0452

AC:

112

AN:

2480

European-Non Finnish (NFE)

AF:

0.0717

AC:

34458

AN:

480732

Other (OTH)

AF:

0.0644

AC:

2163

AN:

33594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2334

4668

7001

9335

11669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.0679

AC:

10345

AN:

152320

Hom.:

359

Cov.:

AF XY:

0.0670

AC XY:

4994

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0666

AC:

2766

AN:

41562

American (AMR)

AF:

0.0483

AC:

740

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

131

AN:

3468

East Asian (EAS)

AF:

0.0599

AC:

311

AN:

5190

South Asian (SAS)

AF:

0.0758

AC:

366

AN:

4830

European-Finnish (FIN)

AF:

0.0655

AC:

696

AN:

10618

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0762

AC:

5186

AN:

68024

Other (OTH)

AF:

0.0629

AC:

133

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

513

1025

1538

2050

2563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0748

Hom.:

Bravo

AF:

0.0642

Asia WGS

AF:

0.100

AC:

349

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.7

(source)

DANN

Benign

0.68

PhyloP100

0.54

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)

0.020

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