dbSNP rs3783465: GADD45A:c.45-63G>A (chr1-67685962-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001924.4(GADD45A):c.45-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000848 in 1,069,434 control chromosomes in the GnomAD database, including 3 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 0.0036 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 3 hom. )

Consequence

GADD45A
NM_001924.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS2

High AC in GnomAd4 at 551 AD gene.

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	UniProt
GADD45A	NM_001924.4	MANE Select	c.45-63G>A	intron	N/A	NP_001915.1	P24522-1
GADD45A	NM_001199741.2		c.45-388G>A	intron	N/A	NP_001186670.1	P24522-2
GADD45A	NM_001199742.2		c.45-63G>A	intron	N/A	NP_001186671.1	A5JUZ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.45-63G>A	intron	N/A	ENSP00000360025.4	P24522-1
GADD45A	ENST00000617962.2	TSL:1	c.45-63G>A	intron	N/A	ENSP00000482814.2	A0A087WZQ0
GADD45A	ENST00000370985.4	TSL:1	c.45-388G>A	intron	N/A	ENSP00000360024.3	P24522-2

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

553

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000955

GnomAD4 exome

AF:

0.000388

AC:

356

AN:

917098

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

161

AN XY:

469002

show subpopulations

African (AFR)

AF:

0.0121

AC:

239

AN:

19712

American (AMR)

AF:

0.000841

AC:

AN:

27346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19852

East Asian (EAS)

AF:

0.00

AC:

AN:

32670

South Asian (SAS)

AF:

0.00

AC:

AN:

66916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49778

Middle Eastern (MID)

AF:

0.00200

AC:

AN:

4506

European-Non Finnish (NFE)

AF:

0.0000672

AC:

AN:

654620

Other (OTH)

AF:

0.000983

AC:

AN:

41698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00362

AC:

551

AN:

152336

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0122

AC:

508

AN:

41578

American (AMR)

AF:

0.00229

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68026

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000488

Hom.:

Bravo

AF:

0.00413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.0

(source)

DANN

Benign

0.84

PhyloP100

0.12

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

4.1

Mutation Taster

=100/0

polymorphism

(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