rs3171012

chr1-67687523-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.385-138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 620,800 control chromosomes in the GnomAD database, including 8,404 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 (2741 hom., cov: 33)
  • Exomes 𝑓: 0.15 (5663 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GADD45A	NM_001924.4	c.385-138T>C		intron_variant		ENST00000370986.9
GADD45A	NM_001199741.2	c.283-138T>C		intron_variant
GADD45A	NM_001199742.2	c.147-138T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GADD45A	ENST00000370986.9	c.385-138T>C		intron_variant		1	NM_001924.4	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27469 AN: 152054 Hom.: 2737 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.146 AC: 68631 AN: 468630 Hom.: 5663 AF XY: 0.144 AC XY: 35859 AN XY: 248310

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.181 AC: 27501 AN: 152170 Hom.: 2741 Cov.: 33 AF XY: 0.182 AC XY: 13552 AN XY: 74398

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0289

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.161

Alfa AF: 0.182 Hom.: 412

Bravo AF: 0.176

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.29
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3171012; hg19: chr1-68153206;