rs3746765

chr20-62889442-C-T

Variant summary

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

The ENST00000395340.5(DIDO1):c.*1489G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 985,224 control chromosomes in the GnomAD database, including 66,421 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 0.42 (14813 hom., cov: 33)
  • Exomes 𝑓: 0.35 (51608 hom.)
• Consequence: DIDO1 ENST00000395340.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

Genes affected

DIDO1 (HGNC:2680): (death inducer-obliterator 1) Apoptosis, a major form of cell death, is an efficient mechanism for eliminating unwanted cells and is of central importance for development and homeostasis in metazoan animals. In mice, the death inducer-obliterator-1 gene is upregulated by apoptotic signals and encodes a cytoplasmic protein that translocates to the nucleus upon apoptotic signal activation. When overexpressed, the mouse protein induced apoptosis in cell lines growing in vitro. This gene is similar to the mouse gene and therefore is thought to be involved in apoptosis. Alternatively spliced transcripts have been found for this gene, encoding multiple isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIDO1	NM_001193369.2	c.3541+1518G>A		intron_variant		ENST00000395343.6
DIDO1	NM_001193370.2	c.*1489G>A		3_prime_UTR_variant	15/15
DIDO1	NM_080797.4	c.*1489G>A		3_prime_UTR_variant	15/15
DIDO1	NM_033081.3	c.3541+1518G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIDO1	ENST00000395340.5	c.*1489G>A		3_prime_UTR_variant	15/15	1		A2
DIDO1	ENST00000395343.6	c.3541+1518G>A		intron_variant		1	NM_001193369.2	P2
DIDO1	ENST00000266070.8	c.3541+1518G>A		intron_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63399 AN: 152004 Hom.: 14778 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.349 AC: 290677 AN: 833102 Hom.: 51608 Cov.: 32 AF XY: 0.350 AC XY: 134462 AN XY: 384714

Gnomad4 AFR exome AF: 0.672

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.417 AC: 63478 AN: 152122 Hom.: 14813 Cov.: 33 AF XY: 0.413 AC XY: 30709 AN XY: 74348

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.368

Alfa AF: 0.363 Hom.: 4104

Bravo AF: 0.427

Asia WGS AF: 0.336 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.3
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3746765; hg19: chr20-61520794;