dbSNP rs11864516: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAO3	NM_022493.3 link	c.440-408T>C		intron_variant	Intron 4 of 10	ENST00000251588.7	NP_071938.1	Q9H6Q4-1
CIAO3	NM_001304799.2 link	c.134-408T>C		intron_variant	Intron 5 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.440-408T>C		intron_variant	Intron 4 of 10	1	NM_022493.3	ENSP00000251588.2		Q9H6Q4-1

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

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

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 v4.3

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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rs11864516

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