dbSNP rs3171012: GADD45A:c.385-138T>C (chr1-67687523-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.385-138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 620,800 control chromosomes in the GnomAD database, including 8,404 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 0.18 ( 2741 hom., cov: 33)

Exomes 𝑓: 0.15 ( 5663 hom. )

Consequence

GADD45A
NM_001924.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Publications

3 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4 link	c.385-138T>C	intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1	P24522-1
GADD45A	NM_001199741.2 link	c.283-138T>C	intron_variant	Intron 2 of 2		NP_001186670.1	P24522-2
GADD45A	NM_001199742.2 link	c.147-138T>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.385-138T>C		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4		P24522-1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27469

AN:

152054

Hom.:

2737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.0496

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.0290

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.146

AC:

68631

AN:

468630

Hom.:

5663

AF XY:

0.144

AC XY:

35859

AN XY:

248310

show subpopulations

African (AFR)

AF:

0.248

AC:

3167

AN:

12784

American (AMR)

AF:

0.128

AC:

2509

AN:

19610

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

2025

AN:

14198

East Asian (EAS)

AF:

0.0269

AC:

842

AN:

31332

South Asian (SAS)

AF:

0.108

AC:

4716

AN:

43850

European-Finnish (FIN)

AF:

0.228

AC:

7319

AN:

32034

Middle Eastern (MID)

AF:

0.192

AC:

386

AN:

2014

European-Non Finnish (NFE)

AF:

0.153

AC:

43711

AN:

285986

Other (OTH)

AF:

0.147

AC:

3956

AN:

26822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2816

5631

8447

11262

14078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.181

AC:

27501

AN:

152170

Hom.:

2741

Cov.:

AF XY:

0.182

AC XY:

13552

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.260

AC:

10772

AN:

41500

American (AMR)

AF:

0.134

AC:

2048

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

513

AN:

3472

East Asian (EAS)

AF:

0.0289

AC:

150

AN:

5188

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4826

European-Finnish (FIN)

AF:

0.235

AC:

2489

AN:

10574

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10550

AN:

67998

Other (OTH)

AF:

0.161

AC:

340

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1163

2327

3490

4654

5817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.166

Hom.:

724

Bravo

AF:

0.176

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.29

(source)

DANN

Benign

0.57

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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