rs3783469

Positions:

• chr1-67686703-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001924.4(GADD45A):​c.384+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 840,512 control chromosomes in the GnomAD database, including 2,067 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 0.068 (359 hom., cov: 34)
  • Exomes 𝑓: 0.067 (1708 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GADD45A	NM_001924.4	c.384+116T>C		intron_variant		ENST00000370986.9
GADD45A	NM_001199741.2	c.282+116T>C		intron_variant
GADD45A	NM_001199742.2	c.146+577T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GADD45A	ENST00000370986.9	c.384+116T>C		intron_variant		1	NM_001924.4	P1

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10342 AN: 152202 Hom.: 361 Cov.: 34

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.0669 AC: 46011 AN: 688192 Hom.: 1708 AF XY: 0.0666 AC XY: 23444 AN XY: 351840

Gnomad4 AFR exome AF: 0.0659

Gnomad4 AMR exome AF: 0.0388

Gnomad4 ASJ exome AF: 0.0355

Gnomad4 EAS exome AF: 0.0360

Gnomad4 SAS exome AF: 0.0670

Gnomad4 FIN exome AF: 0.0635

Gnomad4 NFE exome AF: 0.0717

Gnomad4 OTH exome AF: 0.0644

GnomAD4 genome AF: 0.0679 AC: 10345 AN: 152320 Hom.: 359 Cov.: 34 AF XY: 0.0670 AC XY: 4994 AN XY: 74488

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.0599

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.0655

Gnomad4 NFE AF: 0.0762

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0747 Hom.: 49

Bravo AF: 0.0642

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs3783469; hg19: chr1-68152386;