Genetic Variant GADD45A:c.384+93G>A (chr1-67686680-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_001924.4(GADD45A):c.384+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,108,102 control chromosomes in the GnomAD database, including 163,945 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 0.45 ( 16970 hom., cov: 34)

Exomes 𝑓: 0.55 ( 146975 hom. )

Consequence

GADD45A
NM_001924.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0130

Publications

6 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:

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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 (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4 link	c.384+93G>A	intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1	P24522-1
GADD45A	NM_001199741.2 link	c.282+93G>A	intron_variant	Intron 2 of 2		NP_001186670.1	P24522-2
GADD45A	NM_001199742.2 link	c.146+554G>A	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+93G>A		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4		P24522-1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

68031

AN:

152054

Hom.:

16958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.552

AC:

527575

AN:

955930

Hom.:

146975

AF XY:

0.554

AC XY:

264534

AN XY:

477512

show subpopulations

African (AFR)

AF:

0.197

AC:

4332

AN:

21946

American (AMR)

AF:

0.558

AC:

13392

AN:

24002

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

9463

AN:

17510

East Asian (EAS)

AF:

0.461

AC:

15460

AN:

33522

South Asian (SAS)

AF:

0.597

AC:

36029

AN:

60360

European-Finnish (FIN)

AF:

0.532

AC:

20355

AN:

38226

Middle Eastern (MID)

AF:

0.457

AC:

1400

AN:

3062

European-Non Finnish (NFE)

AF:

0.566

AC:

404313

AN:

714702

Other (OTH)

AF:

0.536

AC:

22831

AN:

42600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

12658

25317

37975

50634

63292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10088

20176

30264

40352

50440

<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:

0.447

AC:

68065

AN:

152172

Hom.:

16970

Cov.:

AF XY:

0.446

AC XY:

33216

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.203

AC:

8449

AN:

41546

American (AMR)

AF:

0.518

AC:

7925

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1820

AN:

3470

East Asian (EAS)

AF:

0.443

AC:

2288

AN:

5164

South Asian (SAS)

AF:

0.568

AC:

2739

AN:

4822

European-Finnish (FIN)

AF:

0.520

AC:

5500

AN:

10568

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37528

AN:

67984

Other (OTH)

AF:

0.487

AC:

1030

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1834

3669

5503

7338

9172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.515

Hom.:

25914

Bravo

AF:

0.437

Asia WGS

AF:

0.476

AC:

1656

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.9

(source)

DANN

Benign

0.72

PhyloP100

0.013

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