Genetic Variant NM_001193369.2:c.1161+23G>C (chr20-62909676-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001193369.2(DIDO1):c.1161+23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,608,262 control chromosomes in the GnomAD database, including 40,196 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 0.25 ( 5120 hom., cov: 33)

Exomes 𝑓: 0.21 ( 35076 hom. )

Consequence

DIDO1
NM_001193369.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

Publications

8 publications found

Variant links:

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]

DIDO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIDO1	NM_001193369.2 link	c.1161+23G>C		intron_variant	Intron 4 of 15	ENST00000395343.6	NP_001180298.1	Q9BTC0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395343.6 link	c.1161+23G>C		intron_variant	Intron 4 of 15	1	NM_001193369.2	ENSP00000378752.1		Q9BTC0-4

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37641

AN:

152112

Hom.:

5105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.247

AC:

61745

AN:

249608

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.211

AC:

306803

AN:

1456032

Hom.:

35076

Cov.:

AF XY:

0.213

AC XY:

153940

AN XY:

723390

show subpopulations

African (AFR)

AF:

0.327

AC:

10885

AN:

33238

American (AMR)

AF:

0.348

AC:

15473

AN:

44458

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

10009

AN:

26004

East Asian (EAS)

AF:

0.344

AC:

13622

AN:

39598

South Asian (SAS)

AF:

0.257

AC:

22079

AN:

85858

European-Finnish (FIN)

AF:

0.122

AC:

6490

AN:

53306

Middle Eastern (MID)

AF:

0.411

AC:

2365

AN:

5748

European-Non Finnish (NFE)

AF:

0.191

AC:

211432

AN:

1107684

Other (OTH)

AF:

0.240

AC:

14448

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13773

27546

41319

55092

68865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7662

15324

22986

30648

38310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37682

AN:

152230

Hom.:

5120

Cov.:

AF XY:

0.244

AC XY:

18189

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.321

AC:

13327

AN:

41540

American (AMR)

AF:

0.291

AC:

4444

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1327

AN:

3470

East Asian (EAS)

AF:

0.337

AC:

1742

AN:

5172

South Asian (SAS)

AF:

0.252

AC:

1217

AN:

4822

European-Finnish (FIN)

AF:

0.131

AC:

1386

AN:

10604

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13199

AN:

68012

Other (OTH)

AF:

0.290

AC:

612

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1479

2958

4438

5917

7396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.235

Hom.:

873

Bravo

AF:

0.270

Asia WGS

AF:

0.296

AC:

1028

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.53

(source)

DANN

Benign

0.44

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over