rs607375

Variant names:

• chr1-67688403-G-C
• rs607375
• NM_001924.4:c.*629G>C

Variant summary

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

The NM_001924.4(GADD45A):​c.*629G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,324 control chromosomes in the GnomAD database, including 31,544 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 0.64 (31489 hom., cov: 33)
  • Exomes 𝑓: 0.66 (55 hom.)
• Consequence: GADD45A NM_001924.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.*629G>C		downstream_gene_variant		ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.*629G>C		downstream_gene_variant			NP_001186670.1
GADD45A	NM_001199742.2	c.*706G>C		downstream_gene_variant			NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.*629G>C		downstream_gene_variant		1	NM_001924.4	ENSP00000360025.4
GADD45A	ENST00000617962.2	c.*629G>C		downstream_gene_variant		1		ENSP00000482814.2

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96737 AN: 151964 Hom.: 31467 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.661 AC: 160 AN: 242 Hom.: 55 AF XY: 0.651 AC XY: 95 AN XY: 146

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.637 AC: 96804 AN: 152082 Hom.: 31489 Cov.: 33 AF XY: 0.634 AC XY: 47181 AN XY: 74360

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.660

Alfa AF: 0.671 Hom.: 4317

Bravo AF: 0.630

Asia WGS AF: 0.653 AC: 2269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs607375; hg19: chr1-68154086;