Genetic Variant CIAO3:c.440-408T>C (chr16-735279-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.440-408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 176,620 control chromosomes in the GnomAD database, including 6,348 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 0.26 ( 5561 hom., cov: 32)

Exomes 𝑓: 0.22 ( 787 hom. )

Consequence

CIAO3
NM_022493.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.694

Publications

14 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 links:

HAGHL (HGNC:14177): (hydroxyacylglutathione hydrolase like) Predicted to enable hydroxyacylglutathione hydrolase activity and metal ion binding activity. Predicted to be involved in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione. [provided by Alliance of Genome Resources, Apr 2022]

HAGHL links:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 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.440-408T>C		intron	N/A	NP_071938.1	Q9H6Q4-1
	CIAO3	NM_001304799.2		c.134-408T>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.440-408T>C	intron	N/A	ENSP00000251588.2	Q9H6Q4-1
CIAO3	ENST00000565341.5	TSL:1	n.319-408T>C	intron	N/A
CIAO3	ENST00000946067.1		c.440-408T>C	intron	N/A	ENSP00000616126.1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39468

AN:

151784

Hom.:

5544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.0389

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.227

GnomAD4 exome

AF:

0.222

AC:

5490

AN:

24718

Hom.:

787

Cov.:

AF XY:

0.224

AC XY:

2842

AN XY:

12680

show subpopulations

African (AFR)

AF:

0.306

AC:

266

AN:

868

American (AMR)

AF:

0.138

AC:

338

AN:

2456

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

107

AN:

672

East Asian (EAS)

AF:

0.0373

AC:

AN:

964

South Asian (SAS)

AF:

0.289

AC:

400

AN:

1382

European-Finnish (FIN)

AF:

0.265

AC:

216

AN:

814

Middle Eastern (MID)

AF:

0.0889

AC:

AN:

European-Non Finnish (NFE)

AF:

0.238

AC:

3803

AN:

15994

Other (OTH)

AF:

0.214

AC:

316

AN:

1478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

205

410

616

821

1026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.260

AC:

39523

AN:

151902

Hom.:

5561

Cov.:

AF XY:

0.258

AC XY:

19177

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.336

AC:

13904

AN:

41396

American (AMR)

AF:

0.175

AC:

2676

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

663

AN:

3470

East Asian (EAS)

AF:

0.0392

AC:

202

AN:

5158

South Asian (SAS)

AF:

0.327

AC:

1572

AN:

4814

European-Finnish (FIN)

AF:

0.260

AC:

2746

AN:

10568

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16976

AN:

67926

Other (OTH)

AF:

0.226

AC:

474

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1473

2947

4420

5894

7367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.247

Hom.:

4097

Bravo

AF:

0.252

Asia WGS

AF:

0.218

AC:

758

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.7

(source)

DANN

Benign

0.29

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over