10-58271700-T-G

Variant names:

• chr10-58271700-T-G
• rs12572520
• NM_018464.5:c.31+2396T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018464.5(CISD1):​c.31+2396T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,150 control chromosomes in the GnomAD database, including 184 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 0.042 (184 hom., cov: 32)
• Consequence: CISD1 NM_018464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CISD1	NM_018464.5	c.31+2396T>G		intron_variant	Intron 1 of 2	ENST00000333926.6	NP_060934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CISD1	ENST00000333926.6	c.31+2396T>G		intron_variant	Intron 1 of 2	1	NM_018464.5	ENSP00000363041.4
CISD1	ENST00000464703.5	n.127+2396T>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6426 AN: 152034 Hom.: 184 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0383

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

GnomAD4 genome AF: 0.0422 AC: 6428 AN: 152150 Hom.: 184 Cov.: 32 AF XY: 0.0445 AC XY: 3309 AN XY: 74366

African (AFR) AF: 0.0213 AC: 885 AN: 41494

American (AMR) AF: 0.0247 AC: 378 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.137 AC: 709 AN: 5164

South Asian (SAS) AF: 0.0952 AC: 458 AN: 4812

European-Finnish (FIN) AF: 0.0528 AC: 559 AN: 10584

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3070 AN: 68010

Other (OTH) AF: 0.0379 AC: 80 AN: 2110

Alfa AF: 0.0213 Hom.: 8

Bravo AF: 0.0381

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.40
PhyloP100		0.24
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: rs12572520; hg19: chr10-60031460;