rs3783468

Variant names:

• chr1-67686680-G-A
• rs3783468
• NM_001924.4:c.384+93G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001924.4(GADD45A):​c.384+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,108,102 control chromosomes in the GnomAD database, including 163,945 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 0.45 (16970 hom., cov: 34)
  • Exomes 𝑓: 0.55 (146975 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.384+93G>A		intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.282+93G>A		intron_variant	Intron 2 of 2		NP_001186670.1
GADD45A	NM_001199742.2	c.146+554G>A		intron_variant	Intron 2 of 2		NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.384+93G>A		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes AF: 0.447 AC: 68031 AN: 152054 Hom.: 16958 Cov.: 34

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.552 AC: 527575 AN: 955930 Hom.: 146975 AF XY: 0.554 AC XY: 264534 AN XY: 477512

African (AFR) AF: 0.197 AC: 4332 AN: 21946

American (AMR) AF: 0.558 AC: 13392 AN: 24002

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 9463 AN: 17510

East Asian (EAS) AF: 0.461 AC: 15460 AN: 33522

South Asian (SAS) AF: 0.597 AC: 36029 AN: 60360

European-Finnish (FIN) AF: 0.532 AC: 20355 AN: 38226

Middle Eastern (MID) AF: 0.457 AC: 1400 AN: 3062

European-Non Finnish (NFE) AF: 0.566 AC: 404313 AN: 714702

Other (OTH) AF: 0.536 AC: 22831 AN: 42600

GnomAD4 genome AF: 0.447 AC: 68065 AN: 152172 Hom.: 16970 Cov.: 34 AF XY: 0.446 AC XY: 33216 AN XY: 74396

African (AFR) AF: 0.203 AC: 8449 AN: 41546

American (AMR) AF: 0.518 AC: 7925 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1820 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2288 AN: 5164

South Asian (SAS) AF: 0.568 AC: 2739 AN: 4822

European-Finnish (FIN) AF: 0.520 AC: 5500 AN: 10568

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37528 AN: 67984

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

Alfa AF: 0.515 Hom.: 25914

Bravo AF: 0.437

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		0.013
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3783468; hg19: chr1-68152363;