1-67686703-T-C

Variant names:

• chr1-67686703-T-C
• rs3783469
• NM_001924.4:c.384+116T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001924.4(GADD45A):​c.384+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 840,512 control chromosomes in the GnomAD database, including 2,067 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 0.068 (359 hom., cov: 34)
  • Exomes 𝑓: 0.067 (1708 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

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+116T>C		intron	N/A	NP_001915.1
	GADD45A	NM_001199741.2		c.282+116T>C		intron	N/A	NP_001186670.1
	GADD45A	NM_001199742.2		c.146+577T>C		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+116T>C		intron	N/A	ENSP00000360025.4
	GADD45A	ENST00000617962.2	TSL:1	c.330+116T>C		intron	N/A	ENSP00000482814.2
	GADD45A	ENST00000370985.4	TSL:1	c.282+116T>C		intron	N/A	ENSP00000360024.3

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10342 AN: 152202 Hom.: 361 Cov.: 34

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.0669 AC: 46011 AN: 688192 Hom.: 1708 AF XY: 0.0666 AC XY: 23444 AN XY: 351840

African (AFR) AF: 0.0659 AC: 1112 AN: 16876

American (AMR) AF: 0.0388 AC: 798 AN: 20564

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 545 AN: 15372

East Asian (EAS) AF: 0.0360 AC: 1159 AN: 32226

South Asian (SAS) AF: 0.0670 AC: 3498 AN: 52228

European-Finnish (FIN) AF: 0.0635 AC: 2166 AN: 34120

Middle Eastern (MID) AF: 0.0452 AC: 112 AN: 2480

European-Non Finnish (NFE) AF: 0.0717 AC: 34458 AN: 480732

Other (OTH) AF: 0.0644 AC: 2163 AN: 33594

GnomAD4 genome AF: 0.0679 AC: 10345 AN: 152320 Hom.: 359 Cov.: 34 AF XY: 0.0670 AC XY: 4994 AN XY: 74488

African (AFR) AF: 0.0666 AC: 2766 AN: 41562

American (AMR) AF: 0.0483 AC: 740 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3468

East Asian (EAS) AF: 0.0599 AC: 311 AN: 5190

South Asian (SAS) AF: 0.0758 AC: 366 AN: 4830

European-Finnish (FIN) AF: 0.0655 AC: 696 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5186 AN: 68024

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0748 Hom.: 51

Bravo AF: 0.0642

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.68
PhyloP100		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3783469; hg19: chr1-68152386;