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

new If you want to explore the variant's impact on the transcript NM_022493.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022493.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIAO3	NM_022493.3	MANE Select	c.67-23T>C		intron	N/A	NP_071938.1	Q9H6Q4-1
	CIAO3	NM_001304799.2		c.-240-23T>C		intron	N/A	NP_001291728.1	Q9H6Q4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CIAO3	ENST00000251588.7	TSL:1 MANE Select	c.67-23T>C	intron	N/A	ENSP00000251588.2	Q9H6Q4-1
CIAO3	ENST00000565341.5	TSL:1	n.79-23T>C	intron	N/A
CIAO3	ENST00000540986.5	TSL:2	c.-263T>C	5_prime_UTR	Exon 1 of 10	ENSP00000444008.1	Q9H6Q4-3

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over