Genetic Variant GADD45A:c.*629G>C (chr1-67688403-G-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.*629G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,324 control chromosomes in the GnomAD database, including 31,544 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 0.64 ( 31489 hom., cov: 33)

Exomes 𝑓: 0.66 ( 55 hom. )

Consequence

GADD45A
NM_001924.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.310

Publications

6 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GADD45A	NM_001924.4 link	c.*629G>C	downstream_gene_variant	ENST00000370986.9	NP_001915.1	P24522-1
GADD45A	NM_001199741.2 link	c.*629G>C	downstream_gene_variant		NP_001186670.1	P24522-2
GADD45A	NM_001199742.2 link	c.*706G>C	downstream_gene_variant		NP_001186671.1	P24522A5JUZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9 link	c.*629G>C		downstream_gene_variant		1	NM_001924.4	ENSP00000360025.4		P24522-1
GADD45A	ENST00000617962.2 link	c.*629G>C		downstream_gene_variant		1		ENSP00000482814.2		A0A087WZQ0

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96737

AN:

151964

Hom.:

31467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.699

Gnomad OTH

AF:

0.658

GnomAD4 exome

AF:

0.661

AC:

160

AN:

242

Hom.:

AF XY:

0.651

AC XY:

AN XY:

146

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.659

AC:

149

AN:

226

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.800

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.637

AC:

96804

AN:

152082

Hom.:

31489

Cov.:

AF XY:

0.634

AC XY:

47181

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.495

AC:

20529

AN:

41442

American (AMR)

AF:

0.686

AC:

10479

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2347

AN:

3472

East Asian (EAS)

AF:

0.567

AC:

2932

AN:

5170

South Asian (SAS)

AF:

0.710

AC:

3429

AN:

4828

European-Finnish (FIN)

AF:

0.685

AC:

7239

AN:

10566

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.699

AC:

47541

AN:

68000

Other (OTH)

AF:

0.660

AC:

1393

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1765

3530

5295

7060

8825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.671

Hom.:

4317

Bravo

AF:

0.630

Asia WGS

AF:

0.653

AC:

2269

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

(source)

DANN

Benign

0.57

PhyloP100

-0.31

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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