rs681673

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-67686705-T-A
• chr1-67686705-T-C
• chr1-67686705-T-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>A 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.384+118T>A		intron_variant	Intron 3 of 3	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.282+118T>A		intron_variant	Intron 2 of 2		NP_001186670.1
GADD45A	NM_001199742.2	c.146+579T>A		intron_variant	Intron 2 of 2		NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.384+118T>A		intron_variant	Intron 3 of 3	1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 666134 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 340764

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: 33030

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;