rs3783472

Variant names:

• chr1-67686875-G-C
• rs3783472
• NM_001924.4:c.384+288G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001924.4(GADD45A):​c.384+288G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 152,334 control chromosomes in the GnomAD database, including 3 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 0.0025 (3 hom., cov: 33)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BS2: High AC in GnomAd4 at 375 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	NM_001924.4	MANE Select	c.384+288G>C		intron	N/A	NP_001915.1
	GADD45A	NM_001199741.2		c.282+288G>C		intron	N/A	NP_001186670.1
	GADD45A	NM_001199742.2		c.146+749G>C		intron	N/A	NP_001186671.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.384+288G>C		intron	N/A	ENSP00000360025.4
	GADD45A	ENST00000617962.2	TSL:1	c.330+288G>C		intron	N/A	ENSP00000482814.2
	GADD45A	ENST00000370985.4	TSL:1	c.282+288G>C		intron	N/A	ENSP00000360024.3

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152216 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00246 AC: 375 AN: 152334 Hom.: 3 Cov.: 33 AF XY: 0.00216 AC XY: 161 AN XY: 74480

African (AFR) AF: 0.00878 AC: 365 AN: 41568

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00287

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.85
PhyloP100		1.6

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: rs3783472; hg19: chr1-68152558;