rs11864516

Positions:

• chr16-735279-A-G
• chr16-735279-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694

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]

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CIAO3	NM_022493.3	c.440-408T>C		intron_variant		ENST00000251588.7	NP_071938.1
CIAO3	NM_001304799.2	c.134-408T>C		intron_variant			NP_001291728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIAO3	ENST00000251588.7	c.440-408T>C		intron_variant		1	NM_022493.3	ENSP00000251588	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39468 AN: 151784 Hom.: 5544 Cov.: 32

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.: 0 AF XY: 0.224 AC XY: 2842 AN XY: 12680

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.0373

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.260 AC: 39523 AN: 151902 Hom.: 5561 Cov.: 32 AF XY: 0.258 AC XY: 19177 AN XY: 74254

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0392

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.226

Alfa AF: 0.246 Hom.: 3401

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
DANN	Benign	0.29

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

LitVar

Other links and lift over

dbSNP: rs11864516; hg19: chr16-785279; COSMIC: COSV52405170; COSMIC: COSV52405170;