rs3752556

chr16-739761-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CIAO3	NM_022493.3	c.67-23T>C		intron_variant		ENST00000251588.7
CIAO3	NM_001304799.2	c.-240-23T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIAO3	ENST00000251588.7	c.67-23T>C		intron_variant		1	NM_022493.3	P1

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

GnomAD3 exomes AF: 0.358 AC: 89403 AN: 249442 Hom.: 21853 AF XY: 0.343 AC XY: 46335 AN XY: 134946

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 SAS exome AF: 0.453

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

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.269

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

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.288

Alfa AF: 0.224 Hom.: 2869

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
Dann	Benign	0.38

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

LitVar

Other links and lift over

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