rs3783478

Variant names:

• chr1-67687768-A-G
• rs3783478
• NM_001924.4:c.492A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001924.4(GADD45A):​c.492A>G​(p.Glu164Glu) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.358 with no splicing effect.
• BS1: 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1330 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	NM_001924.4	MANE Select	c.492A>G	p.Glu164Glu	synonymous	Exon 4 of 4	NP_001915.1
	GADD45A	NM_001199741.2		c.390A>G	p.Glu130Glu	synonymous	Exon 3 of 3	NP_001186670.1
	GADD45A	NM_001199742.2		c.*71A>G		3_prime_UTR	Exon 3 of 3	NP_001186671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.492A>G	p.Glu164Glu	synonymous	Exon 4 of 4	ENSP00000360025.4
	GADD45A	ENST00000617962.2	TSL:1	c.438A>G	p.Glu146Glu	synonymous	Exon 4 of 4	ENSP00000482814.2
	GADD45A	ENST00000370985.4	TSL:1	c.390A>G	p.Glu130Glu	synonymous	Exon 3 of 3	ENSP00000360024.3

Frequencies

GnomAD3 genomes AF: 0.00873 AC: 1328 AN: 152198 Hom.: 17 Cov.: 33

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

GnomAD2 exomes AF: 0.00234 AC: 589 AN: 251284 AF XY: 0.00175

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 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

African (AFR) AF: 0.0288 AC: 952 AN: 33040

American (AMR) AF: 0.00132 AC: 59 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000816 AC: 7 AN: 85828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00155 AC: 7 AN: 4510

European-Non Finnish (NFE) AF: 0.0000246 AC: 27 AN: 1097300

Other (OTH) AF: 0.00188 AC: 112 AN: 59672

GnomAD4 genome AF: 0.00873 AC: 1330 AN: 152316 Hom.: 17 Cov.: 33 AF XY: 0.00836 AC XY: 623 AN XY: 74494

African (AFR) AF: 0.0306 AC: 1270 AN: 41558

American (AMR) AF: 0.00229 AC: 35 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00480 Hom.: 3

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		0.36
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs3783478; hg19: chr1-68153451;