rs3752556

Variant names:

• chr16-739761-A-G
• rs3752556
• NM_022493.3:c.67-23T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 15 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 31

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

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.: 30 AF XY: 0.245 AC XY: 177161 AN XY: 724574

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

GnomAD4 genome AF: 0.343 AC: 52167 AN: 151988 Hom.: 11500 Cov.: 31 AF XY: 0.355 AC XY: 26399 AN XY: 74276

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: 80 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12393 AN: 67924

Other (OTH) AF: 0.288 AC: 607 AN: 2110

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
DANN	Benign	0.38
PhyloP100		-0.068
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3752556; hg19: chr16-789761; COSMIC: COSV52403566; COSMIC: COSV52403566;