Genetic Variant CISD1:c.-140C>T (chr10-58269134-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018464.5(CISD1):c.-140C>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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

23 publications found

Variant links:

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]

CISD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CISD1	NM_018464.5 link	c.-140C>T		upstream_gene_variant		ENST00000333926.6	NP_060934.1	Q9NZ45A0A024QZN7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CISD1	ENST00000333926.6 link	c.-140C>T		upstream_gene_variant		1	NM_018464.5	ENSP00000363041.4		Q9NZ45
CISD1	ENST00000464703.5 link	n.-44C>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51398

AN:

152038

Hom.:

10927

Cov.:

show subpopulations

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.:

AF XY:

0.248

AC XY:

90418

AN XY:

364252

show subpopulations

African (AFR)

AF:

0.614

AC:

11537

AN:

18786

American (AMR)

AF:

0.199

AC:

7020

AN:

35260

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

4419

AN:

20284

East Asian (EAS)

AF:

0.415

AC:

13866

AN:

33444

South Asian (SAS)

AF:

0.277

AC:

18033

AN:

65170

European-Finnish (FIN)

AF:

0.234

AC:

8151

AN:

34780

Middle Eastern (MID)

AF:

0.216

AC:

579

AN:

2678

European-Non Finnish (NFE)

AF:

0.220

AC:

97027

AN:

441022

Other (OTH)

AF:

0.257

AC:

8941

AN:

34822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

6271

12542

18812

25083

31354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1802

3604

5406

7208

9010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.338

AC:

51485

AN:

152156

Hom.:

10961

Cov.:

AF XY:

0.338

AC XY:

25133

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.607

AC:

25175

AN:

41490

American (AMR)

AF:

0.236

AC:

3606

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3472

East Asian (EAS)

AF:

0.446

AC:

2306

AN:

5168

South Asian (SAS)

AF:

0.277

AC:

1334

AN:

4824

European-Finnish (FIN)

AF:

0.219

AC:

2328

AN:

10606

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15103

AN:

67974

Other (OTH)

AF:

0.284

AC:

599

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1610

3220

4831

6441

8051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.264

Hom.:

13281

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

(source)

DANN

Benign

0.75

PhyloP100

0.027

PromoterAI

-0.066

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over