1-67686705-T-G

Variant names:

• chr1-67686705-T-G
• rs681673
• NM_001924.4:c.384+118T>G

Variant summary

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

The NM_001924.4(GADD45A):​c.384+118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 7 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=-0.83).

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+118T>G		intron	N/A	NP_001915.1
	GADD45A	NM_001199741.2		c.282+118T>G		intron	N/A	NP_001186670.1
	GADD45A	NM_001199742.2		c.146+579T>G		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+118T>G		intron	N/A	ENSP00000360025.4
	GADD45A	ENST00000617962.2	TSL:1	c.330+118T>G		intron	N/A	ENSP00000482814.2
	GADD45A	ENST00000370985.4	TSL:1	c.282+118T>G		intron	N/A	ENSP00000360024.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 666136 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 340766

African (AFR) AF: 0.00 AC: 0 AN: 16422

American (AMR) AF: 0.00 AC: 0 AN: 20468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15184

East Asian (EAS) AF: 0.00 AC: 0 AN: 32122

South Asian (SAS) AF: 0.00 AC: 0 AN: 51594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2424

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 461922

Other (OTH) AF: 0.00 AC: 0 AN: 33032

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.67
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs681673; hg19: chr1-68152388;