chr10-58289260-G-A

Variant names:

• chr10-58289260-G-A
• rs2590370
• NM_018464.5:c.*1610G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CISD1	NM_018464.5	c.*1610G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000333926.6	NP_060934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CISD1	ENST00000333926.6	c.*1610G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_018464.5	ENSP00000363041.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.227 AC: 30 AN: 132

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.607 AC: 25155 AN: 41438

American (AMR) AF: 0.236 AC: 3593 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 785 AN: 3458

East Asian (EAS) AF: 0.446 AC: 2309 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4818

European-Finnish (FIN) AF: 0.220 AC: 2320 AN: 10542

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15045 AN: 67784

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.244 Hom.: 1379

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
PhyloP100		0.52
Mutation Taster		=100/0	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: rs2590370; hg19: chr10-60049020;