rs11812882

chr10-58282865-T-C

Variant summary

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

The NM_018464.5(CISD1):c.238-4696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,224 control chromosomes in the GnomAD database, including 327 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 0.061 (327 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CISD1 NM_018464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CISD1	NM_018464.5	c.238-4696T>C		intron_variant		ENST00000333926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CISD1	ENST00000333926.6	c.238-4696T>C		intron_variant		1	NM_018464.5	P1
CISD1	ENST00000464703.5	n.429-4696T>C		intron_variant, non_coding_transcript_variant		5
CISD1	ENST00000488388.2	n.259-34T>C		intron_variant, non_coding_transcript_variant		5
CISD1	ENST00000489785.5	n.306-4696T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9197 AN: 152104 Hom.: 325 Cov.: 32

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.0605 AC: 9212 AN: 152222 Hom.: 327 Cov.: 32 AF XY: 0.0575 AC XY: 4279 AN XY: 74430

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0620 Hom.: 284

Bravo AF: 0.0640

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.7
Dann	Benign	0.48

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: rs11812882; hg19: chr10-60042625;