rs3746765

Variant names:

• chr20-62889442-C-T
• rs3746765
• ENST00000395340.5:c.*1489G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DIDO1	NM_001193369.2	c.3541+1518G>A		intron_variant	Intron 15 of 15	ENST00000395343.6	NP_001180298.1
DIDO1	NM_001193370.2	c.*1489G>A		3_prime_UTR_variant	Exon 15 of 15		NP_001180299.1
DIDO1	NM_080797.4	c.*1489G>A		3_prime_UTR_variant	Exon 15 of 15		NP_542987.2
DIDO1	NM_033081.3	c.3541+1518G>A		intron_variant	Intron 15 of 15		NP_149072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395340.5	c.*1489G>A		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000378749.1
DIDO1	ENST00000395343.6	c.3541+1518G>A		intron_variant	Intron 15 of 15	1	NM_001193369.2	ENSP00000378752.1
DIDO1	ENST00000266070.8	c.3541+1518G>A		intron_variant	Intron 15 of 15	5		ENSP00000266070.4

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

African (AFR) AF: 0.672 AC: 10614 AN: 15786

American (AMR) AF: 0.284 AC: 279 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1666 AN: 5152

East Asian (EAS) AF: 0.301 AC: 1091 AN: 3630

South Asian (SAS) AF: 0.299 AC: 4926 AN: 16460

European-Finnish (FIN) AF: 0.314 AC: 88 AN: 280

Middle Eastern (MID) AF: 0.346 AC: 560 AN: 1620

European-Non Finnish (NFE) AF: 0.344 AC: 261871 AN: 761896

Other (OTH) AF: 0.351 AC: 9582 AN: 27294

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

African (AFR) AF: 0.647 AC: 26866 AN: 41494

American (AMR) AF: 0.341 AC: 5219 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1582 AN: 5178

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4826

European-Finnish (FIN) AF: 0.296 AC: 3124 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22994 AN: 67980

Other (OTH) AF: 0.368 AC: 779 AN: 2116

Alfa AF: 0.369 Hom.: 5121

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
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746765; hg19: chr20-61520794;