Genetic Variant GADD45A:c.385-73_385-65delTTCTCCTCA (chr1-67687587-TTTCTCCTCA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001924.4(GADD45A):c.385-73_385-65delTTCTCCTCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 916,474 control chromosomes in the GnomAD database, including 231 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 163 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 68 hom. )

Consequence

GADD45A
NM_001924.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GADD45A	NM_001924.4 link	c.385-73_385-65delTTCTCCTCA	intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2 link	c.283-73_283-65delTTCTCCTCA	intron_variant	Intron 2 of 2		NP_001186670.1
GADD45A	NM_001199742.2 link	c.147-73_147-65delTTCTCCTCA	intron_variant	Intron 2 of 2		NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9 link	c.385-73_385-65delTTCTCCTCA		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3634

AN:

152164

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0834

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0158

GnomAD4 exome

AF:

0.00299

AC:

2285

AN:

764194

Hom.:

AF XY:

0.00252

AC XY:

1010

AN XY:

401442

show subpopulations

African (AFR)

AF:

0.0895

AC:

1649

AN:

18432

American (AMR)

AF:

0.00496

AC:

173

AN:

34850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20548

East Asian (EAS)

AF:

0.00

AC:

AN:

32806

South Asian (SAS)

AF:

0.000197

AC:

AN:

65870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46592

Middle Eastern (MID)

AF:

0.00754

AC:

AN:

2784

European-Non Finnish (NFE)

AF:

0.000323

AC:

163

AN:

505370

Other (OTH)

AF:

0.00720

AC:

266

AN:

36942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

106

212

318

424

530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0239

AC:

3636

AN:

152280

Hom.:

163

Cov.:

AF XY:

0.0229

AC XY:

1705

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0832

AC:

3455

AN:

41520

American (AMR)

AF:

0.00758

AC:

116

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68030

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

167

335

502

670

837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0193

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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