Genetic Variant NM_001924.4: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:

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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

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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