1-67688525-G-A

Variant names:

• chr1-67688525-G-A
• rs3783483
• NM_001924.4:c.*751G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001924.4(GADD45A):​c.*751G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 152,324 control chromosomes in the GnomAD database, including 11 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 0.0048 (11 hom., cov: 33)
• Consequence: GADD45A NM_001924.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 1 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=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00483 (735/152324) while in subpopulation AFR AF = 0.0165 (684/41564). AF 95% confidence interval is 0.0154. There are 11 homozygotes in GnomAd4. There are 336 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 735 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001924.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	NM_001924.4	MANE Select	c.*751G>A		downstream_gene	N/A	NP_001915.1
	GADD45A	NM_001199741.2		c.*751G>A		downstream_gene	N/A	NP_001186670.1
	GADD45A	NM_001199742.2		c.*828G>A		downstream_gene	N/A	NP_001186671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.*751G>A		downstream_gene	N/A	ENSP00000360025.4
	GADD45A	ENST00000617962.2	TSL:1	c.*751G>A		downstream_gene	N/A	ENSP00000482814.2

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 733 AN: 152206 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00483 AC: 735 AN: 152324 Hom.: 11 Cov.: 33 AF XY: 0.00451 AC XY: 336 AN XY: 74490

African (AFR) AF: 0.0165 AC: 684 AN: 41564

American (AMR) AF: 0.00235 AC: 36 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68034

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00522

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.65
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs3783483; hg19: chr1-68154208;