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GeneBe

rs3783478

chr1-67687768-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_001924.4(GADD45A):c.492A>G(p.Glu164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,596,402 control chromosomes in the GnomAD database, including 36 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 0.0087 ( 17 hom., cov: 33)
Exomes 𝑓: 0.00081 ( 19 hom. )

Consequence

GADD45A
NM_001924.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.358
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.358 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00873 (1330/152316) while in subpopulation AFR AF= 0.0306 (1270/41558). AF 95% confidence interval is 0.0292. There are 17 homozygotes in gnomad4. There are 623 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1328 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GADD45ANM_001924.4 linkuse as main transcriptc.492A>G p.Glu164= synonymous_variant 4/4 ENST00000370986.9
GADD45ANM_001199741.2 linkuse as main transcriptc.390A>G p.Glu130= synonymous_variant 3/3
GADD45ANM_001199742.2 linkuse as main transcriptc.*71A>G 3_prime_UTR_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GADD45AENST00000370986.9 linkuse as main transcriptc.492A>G p.Glu164= synonymous_variant 4/41 NM_001924.4 P1P24522-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00873
AC:
1328
AN:
152198
Hom.:
17
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0306
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.00234
AC:
589
AN:
251284
Hom.:
15
AF XY:
0.00175
AC XY:
238
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.0325
Gnomad AMR exome
AF:
0.00130
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000806
AC:
1164
AN:
1444086
Hom.:
19
Cov.:
26
AF XY:
0.000688
AC XY:
495
AN XY:
719538
show subpopulations
Gnomad4 AFR exome
AF:
0.0288
Gnomad4 AMR exome
AF:
0.00132
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000816
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000246
Gnomad4 OTH exome
AF:
0.00188
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00873
AC:
1330
AN:
152316
Hom.:
17
Cov.:
33
AF XY:
0.00836
AC XY:
623
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0306
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00489
Hom.:
1
Bravo
AF:
0.00983
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
7.8
Dann
Benign
0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3783478; hg19: chr1-68153451; API