1-67686002-C-T

Variant names:

• chr1-67686002-C-T
• rs3783466
• ENST00000484245.1:n.327C>T

Variant summary

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

The ENST00000484245.1(GADD45A):​n.327C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,552,032 control chromosomes in the GnomAD database, including 17,744 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 0.18 (2712 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15032 hom.)
• Consequence: GADD45A ENST00000484245.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.45-23C>T		intron_variant	Intron 1 of 3	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.45-348C>T		intron_variant	Intron 1 of 2		NP_001186670.1
GADD45A	NM_001199742.2	c.45-23C>T		intron_variant	Intron 1 of 2		NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.45-23C>T		intron_variant	Intron 1 of 3	1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27103 AN: 152014 Hom.: 2703 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.139 AC: 30564 AN: 220412 AF XY: 0.136

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.0237

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.141 AC: 196859 AN: 1399900 Hom.: 15032 Cov.: 24 AF XY: 0.140 AC XY: 97336 AN XY: 696844

African (AFR) AF: 0.265 AC: 8068 AN: 30420

American (AMR) AF: 0.114 AC: 4581 AN: 40132

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3713 AN: 24740

East Asian (EAS) AF: 0.0269 AC: 1003 AN: 37246

South Asian (SAS) AF: 0.0902 AC: 7473 AN: 82846

European-Finnish (FIN) AF: 0.222 AC: 11678 AN: 52546

Middle Eastern (MID) AF: 0.173 AC: 966 AN: 5570

European-Non Finnish (NFE) AF: 0.141 AC: 151102 AN: 1068480

Other (OTH) AF: 0.143 AC: 8275 AN: 57920

GnomAD4 genome AF: 0.178 AC: 27142 AN: 152132 Hom.: 2712 Cov.: 33 AF XY: 0.179 AC XY: 13308 AN XY: 74354

African (AFR) AF: 0.266 AC: 11023 AN: 41504

American (AMR) AF: 0.132 AC: 2013 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3470

East Asian (EAS) AF: 0.0288 AC: 149 AN: 5166

South Asian (SAS) AF: 0.0907 AC: 438 AN: 4828

European-Finnish (FIN) AF: 0.224 AC: 2372 AN: 10584

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10189 AN: 67964

Other (OTH) AF: 0.162 AC: 340 AN: 2104

Alfa AF: 0.150 Hom.: 2789

Bravo AF: 0.175

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.95
PhyloP100		1.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		4.1
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: rs3783466; hg19: chr1-68151685;