1-67686297-T-G

Position:

• chr1-67686297-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001924.4(GADD45A):​c.147-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,539,056 control chromosomes in the GnomAD database, including 547,885 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 0.80 (49699 hom., cov: 34)
  • Exomes 𝑓: 0.85 (498186 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968

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]

GADD45A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GADD45A	NM_001924.4	c.147-53T>G		intron_variant		ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2	c.45-53T>G		intron_variant			NP_001186670.1
GADD45A	NM_001199742.2	c.146+171T>G		intron_variant			NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9	c.147-53T>G		intron_variant		1	NM_001924.4	ENSP00000360025.4

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122094 AN: 152054 Hom.: 49658 Cov.: 34

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.812

GnomAD4 exome AF: 0.846 AC: 1172987 AN: 1386884 Hom.: 498186 Cov.: 23 AF XY: 0.846 AC XY: 581315 AN XY: 687158

Gnomad4 AFR exome AF: 0.676

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.844

Gnomad4 FIN exome AF: 0.926

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.829

GnomAD4 genome AF: 0.803 AC: 122194 AN: 152172 Hom.: 49699 Cov.: 34 AF XY: 0.804 AC XY: 59843 AN XY: 74406

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.814

Alfa AF: 0.841 Hom.: 6782

Bravo AF: 0.786

Asia WGS AF: 0.746 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.9
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs2759219; hg19: chr1-68151980; COSMIC: COSV63974744;