10-58269134-C-T

Variant summary

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

The 10-58269134-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 838,402 control chromosomes in the GnomAD database, including 34,279 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 (10961 hom., cov: 33)
  • Exomes 𝑓: 0.25 (23318 hom.)
• Consequence: CISD1 NM_018464.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CISD1	NM_018464.5			upstream_gene_variant		ENST00000333926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CISD1	ENST00000333926.6			upstream_gene_variant		1	NM_018464.5	P1
CISD1	ENST00000464703.5			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51398 AN: 152038 Hom.: 10927 Cov.: 33

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: 0.219

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.247 AC: 169573 AN: 686246 Hom.: 23318 Cov.: 9 AF XY: 0.248 AC XY: 90418 AN XY: 364252

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.338 AC: 51485 AN: 152156 Hom.: 10961 Cov.: 33 AF XY: 0.338 AC XY: 25133 AN XY: 74400

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: 0.219

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.284

Alfa AF: 0.224 Hom.: 5030

Bravo AF: 0.353

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	8.8
Dann	Benign	0.75

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: rs2251039; hg19: chr10-60028894; COSMIC: COSV61703355; COSMIC: COSV61703355;