dbSNP rs3783465: GADD45A:n.287G>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 ENST00000484245.1(GADD45A):n.287G>A variant causes a non coding transcript exon 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
ENST00000484245.1 non_coding_transcript_exon

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4 link	c.45-63G>A	intron_variant	Intron 1 of 3	ENST00000370986.9	NP_001915.1	P24522-1
GADD45A	NM_001199741.2 link	c.45-388G>A	intron_variant	Intron 1 of 2		NP_001186670.1	P24522-2
GADD45A	NM_001199742.2 link	c.45-63G>A	intron_variant	Intron 1 of 2		NP_001186671.1	P24522A5JUZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9 link	c.45-63G>A		intron_variant	Intron 1 of 3	1	NM_001924.4	ENSP00000360025.4		P24522-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over