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:

Genome browser will be placed here

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018464.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CISD1	NM_018464.5	MANE Select	c.-140C>T		upstream_gene	N/A	NP_060934.1	Q9NZ45

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CISD1	ENST00000333926.6	TSL:1 MANE Select	c.-140C>T	upstream_gene	N/A	ENSP00000363041.4	Q9NZ45
CISD1	ENST00000948691.1		c.-140C>T	upstream_gene	N/A	ENSP00000618750.1
CISD1	ENST00000865195.1		c.-140C>T	upstream_gene	N/A	ENSP00000535254.1

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over