ENST00000484245.1:n.287G>C

Variant names:

• chr1-67685962-G-C
• rs3783465
• ENST00000484245.1:n.287G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000484245.1(GADD45A):​n.287G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 917,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: GADD45A ENST00000484245.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.45-63G>C		intron_variant	Intron 1 of 3	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.45-388G>C		intron_variant	Intron 1 of 2		NP_001186670.1
GADD45A	NM_001199742.2	c.45-63G>C		intron_variant	Intron 1 of 2		NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.45-63G>C		intron_variant	Intron 1 of 3	1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 917102 Hom.: 0 Cov.: 12 AF XY: 0.00000213 AC XY: 1 AN XY: 469004

African (AFR) AF: 0.00 AC: 0 AN: 19714

American (AMR) AF: 0.00 AC: 0 AN: 27346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19852

East Asian (EAS) AF: 0.00 AC: 0 AN: 32670

South Asian (SAS) AF: 0.00 AC: 0 AN: 66916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4506

European-Non Finnish (NFE) AF: 0.00000153 AC: 1 AN: 654622

Other (OTH) AF: 0.00 AC: 0 AN: 41698

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		0.12
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		4.1

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: rs3783465; hg19: chr1-68151645;