rs2590370

chr10-58289260-G-Achr10-58289260-G-C

Variant summary

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

The NM_018464.5(CISD1):c.*1610G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,910 control chromosomes in the GnomAD database, including 10,940 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 (10936 hom., cov: 32)
  • Exomes 𝑓: 0.23 (4 hom.)
• Consequence: CISD1 NM_018464.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

Genes affected

CISD1 (HGNC:30880): (CDGSH iron sulfur domain 1) This gene encodes a protein with a CDGSH iron-sulfur domain and has been shown to bind a redox-active [2Fe-2S] cluster. The encoded protein has been localized to the outer membrane of mitochondria and is thought to play a role in regulation of oxidation. Genes encoding similar proteins are located on chromosomes 4 and 17, and a pseudogene of this gene is located on chromosome 2. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CISD1	NM_018464.5	c.*1610G>A		3_prime_UTR_variant	3/3	ENST00000333926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CISD1	ENST00000333926.6	c.*1610G>A		3_prime_UTR_variant	3/3	1	NM_018464.5	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51306 AN: 151660 Hom.: 10904 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.227 AC: 30 AN: 132 Hom.: 4 Cov.: 0 AF XY: 0.237 AC XY: 18 AN XY: 76

Gnomad4 EAS exome AF: 0.227

GnomAD4 genome AF: 0.339 AC: 51391 AN: 151778 Hom.: 10936 Cov.: 32 AF XY: 0.338 AC XY: 25070 AN XY: 74154

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.286

Alfa AF: 0.211 Hom.: 882

Bravo AF: 0.352

Asia WGS AF: 0.322 AC: 1123 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.8
Dann	Benign	0.65

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: rs2590370; hg19: chr10-60049020;