rs532446

Variant names:

• chr1-67686755-C-T
• rs532446
• NM_001924.4:c.384+168C>T

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+168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,126 control chromosomes in the GnomAD database, including 30,290 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 0.62 (30290 hom., cov: 33)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 12 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 = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.384+168C>T		intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.282+168C>T		intron_variant	Intron 2 of 2		NP_001186670.1
GADD45A	NM_001199742.2	c.146+629C>T		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+168C>T		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93666 AN: 152008 Hom.: 30273 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.616 AC: 93725 AN: 152126 Hom.: 30290 Cov.: 33 AF XY: 0.616 AC XY: 45785 AN XY: 74370

African (AFR) AF: 0.405 AC: 16790 AN: 41490

American (AMR) AF: 0.678 AC: 10371 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2364 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3038 AN: 5168

South Asian (SAS) AF: 0.719 AC: 3462 AN: 4816

European-Finnish (FIN) AF: 0.696 AC: 7367 AN: 10582

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48057 AN: 67984

Other (OTH) AF: 0.646 AC: 1364 AN: 2112

Alfa AF: 0.674 Hom.: 12166

Bravo AF: 0.604

Asia WGS AF: 0.652 AC: 2267 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	8.0
DANN	Benign	0.61
PhyloP100		-0.29
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: rs532446; hg19: chr1-68152438;