dbSNP rs3752556: CIAO3:c.67-23T>C (chr16-739761-A-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_022493.3(CIAO3):c.67-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,609,108 control chromosomes in the GnomAD database, including 69,549 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 0.34 ( 11500 hom., cov: 31)

Exomes 𝑓: 0.24 ( 58049 hom. )

Consequence

CIAO3
NM_022493.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

Publications

15 publications found

Variant links:

Genes affected

CIAO3 (HGNC:14179): (cytosolic iron-sulfur assembly component 3) Predicted to enable 4 iron, 4 sulfur cluster binding activity. Involved in several processes, including iron-sulfur cluster assembly; oxygen homeostasis; and response to hypoxia. Part of CIA complex. [provided by Alliance of Genome Resources, Apr 2022]

CIAO3 Gene-Disease associations (from GenCC):

pulmonary arteriovenous malformation
Inheritance: AR Classification: LIMITED Submitted by: Illumina

CIAO3 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAO3	NM_022493.3 link	c.67-23T>C		intron_variant	Intron 1 of 10	ENST00000251588.7	NP_071938.1	Q9H6Q4-1
CIAO3	NM_001304799.2 link	c.-240-23T>C		intron_variant	Intron 2 of 11		NP_001291728.1	Q9H6Q4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAO3	ENST00000251588.7 link	c.67-23T>C		intron_variant	Intron 1 of 10	1	NM_022493.3	ENSP00000251588.2		Q9H6Q4-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52096

AN:

151870

Hom.:

11478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.283

GnomAD2 exomes

AF:

0.358

AC:

89403

AN:

249442

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.542

Gnomad AMR exome

AF:

0.613

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.821

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.242

AC:

351919

AN:

1457120

Hom.:

58049

Cov.:

AF XY:

0.245

AC XY:

177161

AN XY:

724574

show subpopulations

African (AFR)

AF:

0.535

AC:

17852

AN:

33394

American (AMR)

AF:

0.591

AC:

26352

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4948

AN:

25958

East Asian (EAS)

AF:

0.792

AC:

31413

AN:

39658

South Asian (SAS)

AF:

0.447

AC:

38421

AN:

86040

European-Finnish (FIN)

AF:

0.307

AC:

16281

AN:

53050

Middle Eastern (MID)

AF:

0.210

AC:

1211

AN:

5756

European-Non Finnish (NFE)

AF:

0.180

AC:

199235

AN:

1108438

Other (OTH)

AF:

0.269

AC:

16206

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12846

25692

38538

51384

64230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7738

15476

23214

30952

38690

<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:

0.343

AC:

52167

AN:

151988

Hom.:

11500

Cov.:

AF XY:

0.355

AC XY:

26399

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.531

AC:

22018

AN:

41486

American (AMR)

AF:

0.433

AC:

6607

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

671

AN:

3468

East Asian (EAS)

AF:

0.805

AC:

4137

AN:

5142

South Asian (SAS)

AF:

0.462

AC:

2222

AN:

4808

European-Finnish (FIN)

AF:

0.311

AC:

3290

AN:

10580

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12393

AN:

67924

Other (OTH)

AF:

0.288

AC:

607

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1546

3092

4637

6183

7729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.222

Hom.:

3061

Bravo

AF:

0.362

Asia WGS

AF:

0.597

AC:

2072

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.15

(source)

DANN

Benign

0.38

PhyloP100

-0.068

Mutation Taster

=300/0

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