rs3046000

Positions:

• chr1-67687587-TTTCTCCTCA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001924.4(GADD45A):​c.385-73_385-65delTTCTCCTCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 916,474 control chromosomes in the GnomAD database, including 231 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (163 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (68 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.385-73_385-65delTTCTCCTCA		intron_variant		ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.283-73_283-65delTTCTCCTCA		intron_variant			NP_001186670.1
GADD45A	NM_001199742.2	c.147-73_147-65delTTCTCCTCA		intron_variant			NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.385-73_385-65delTTCTCCTCA		intron_variant		1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3634 AN: 152164 Hom.: 162 Cov.: 33

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00299 AC: 2285 AN: 764194 Hom.: 68 AF XY: 0.00252 AC XY: 1010 AN XY: 401442

Gnomad4 AFR exome AF: 0.0895

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000323

Gnomad4 OTH exome AF: 0.00720

GnomAD4 genome AF: 0.0239 AC: 3636 AN: 152280 Hom.: 163 Cov.: 33 AF XY: 0.0229 AC XY: 1705 AN XY: 74476

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0193 Hom.: 15

Bravo AF: 0.0269

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3046000; hg19: chr1-68153270;