chr1-67686705-T-C

Position:

• chr1-67686705-T-C

Variant summary

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

The NM_001924.4(GADD45A):​c.384+118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 817,338 control chromosomes in the GnomAD database, including 192,812 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 0.62 (30262 hom., cov: 33)
  • Exomes 𝑓: 0.70 (162550 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GADD45A	NM_001924.4	c.384+118T>C		intron_variant		ENST00000370986.9
GADD45A	NM_001199741.2	c.282+118T>C		intron_variant
GADD45A	NM_001199742.2	c.146+579T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GADD45A	ENST00000370986.9	c.384+118T>C		intron_variant		1	NM_001924.4	P1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93606 AN: 152010 Hom.: 30245 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.696 AC: 463003 AN: 665210 Hom.: 162550 AF XY: 0.698 AC XY: 237496 AN XY: 340316

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.616 AC: 93664 AN: 152128 Hom.: 30262 Cov.: 33 AF XY: 0.615 AC XY: 45755 AN XY: 74384

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.645

Alfa AF: 0.576 Hom.: 1883

Bravo AF: 0.604

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.67

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: rs681673; hg19: chr1-68152388;