rs60599

Positions:

• chr15-64092233-A-C
• chr15-64092233-A-T

Variant summary

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

The ENST00000300030.8(CIAO2A):​c.124+1412T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,206 control chromosomes in the GnomAD database, including 65,968 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 0.92 (65968 hom., cov: 31)
• Consequence: CIAO2A ENST00000300030.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

Genes affected

CIAO2A (HGNC:26235): (cytosolic iron-sulfur assembly component 2A) Predicted to enable metal ion binding activity. Involved in iron-sulfur cluster assembly and protein maturation by iron-sulfur cluster transfer. Located in cytosol and nucleoplasm. 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIAO2A	NM_032231.7	c.124+1412T>G		intron_variant		ENST00000300030.8	NP_115607.1
CIAO2A	NM_001014812.3	c.124+1412T>G		intron_variant			NP_001014812.1
CIAO2A	NM_001289108.2	c.124+1412T>G		intron_variant			NP_001276037.1
CIAO2A	NR_110310.2	n.194+1412T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIAO2A	ENST00000300030.8	c.124+1412T>G		intron_variant		1	NM_032231.7	ENSP00000300030	P1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140600 AN: 152088 Hom.: 65925 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.945

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.924 AC: 140696 AN: 152206 Hom.: 65968 Cov.: 31 AF XY: 0.927 AC XY: 69007 AN XY: 74422

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.946

Alfa AF: 0.970 Hom.: 20424

Bravo AF: 0.914

Asia WGS AF: 0.984 AC: 3421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.67

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: rs60599; hg19: chr15-64384432;