Genetic Variant GADD45A:c.384+118T>C (chr1-67686705-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+118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 817,338 control chromosomes in the GnomAD database, including 192,812 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 0.62 ( 30262 hom., cov: 33)

Exomes 𝑓: 0.70 ( 162550 hom. )

Consequence

GADD45A
NM_001924.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

7 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001924.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GADD45A	NM_001924.4	MANE Select	c.384+118T>C	intron	N/A	NP_001915.1
GADD45A	NM_001199741.2		c.282+118T>C	intron	N/A	NP_001186670.1
GADD45A	NM_001199742.2		c.146+579T>C	intron	N/A	NP_001186671.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.384+118T>C	intron	N/A	ENSP00000360025.4
GADD45A	ENST00000617962.2	TSL:1	c.330+118T>C	intron	N/A	ENSP00000482814.2
GADD45A	ENST00000370985.4	TSL:1	c.282+118T>C	intron	N/A	ENSP00000360024.3

Frequencies

GnomAD3 genomes

AF:

0.616

AC:

93606

AN:

152010

Hom.:

30245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.682

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.696

AC:

463003

AN:

665210

Hom.:

162550

AF XY:

0.698

AC XY:

237496

AN XY:

340316

show subpopulations

African (AFR)

AF:

0.406

AC:

6650

AN:

16386

American (AMR)

AF:

0.715

AC:

14628

AN:

20452

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

10425

AN:

15172

East Asian (EAS)

AF:

0.577

AC:

18518

AN:

32102

South Asian (SAS)

AF:

0.737

AC:

38017

AN:

51562

European-Finnish (FIN)

AF:

0.698

AC:

22991

AN:

32950

Middle Eastern (MID)

AF:

0.581

AC:

1409

AN:

2424

European-Non Finnish (NFE)

AF:

0.711

AC:

327948

AN:

461160

Other (OTH)

AF:

0.679

AC:

22417

AN:

33002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7640

15281

22921

30562

38202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5330

10660

15990

21320

26650

<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:

0.616

AC:

93664

AN:

152128

Hom.:

30262

Cov.:

AF XY:

0.615

AC XY:

45755

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.403

AC:

16725

AN:

41492

American (AMR)

AF:

0.677

AC:

10360

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

2367

AN:

3472

East Asian (EAS)

AF:

0.586

AC:

3027

AN:

5162

South Asian (SAS)

AF:

0.719

AC:

3472

AN:

4826

European-Finnish (FIN)

AF:

0.696

AC:

7363

AN:

10572

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.707

AC:

48074

AN:

67990

Other (OTH)

AF:

0.645

AC:

1363

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1784

3567

5351

7134

8918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.576

Hom.:

1883

Bravo

AF:

0.604

Asia WGS

AF:

0.652

AC:

2268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.8

(source)

DANN

Benign

0.67

PhyloP100

-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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over