rs223331

Positions:

• chr4-102872408-T-A
• chr4-102872408-T-C

Variant summary

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

The ENST00000273986.10(CISD2):​c.103+3221T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,038 control chromosomes in the GnomAD database, including 10,693 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 0.37 (10693 hom., cov: 32)
• Consequence: CISD2 ENST00000273986.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

Genes affected

CISD2 (HGNC:24212): (CDGSH iron sulfur domain 2) The protein encoded by this gene is a zinc finger protein that localizes to the endoplasmic reticulum. The encoded protein binds an iron/sulfur cluster and may be involved in calcium homeostasis. Defects in this gene are a cause of Wolfram syndrome 2. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CISD2	NM_001008388.5	c.103+3221T>A		intron_variant		ENST00000273986.10	NP_001008389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CISD2	ENST00000273986.10	c.103+3221T>A		intron_variant		1	NM_001008388.5	ENSP00000273986	P1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56629 AN: 151920 Hom.: 10685 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.373 AC: 56663 AN: 152038 Hom.: 10693 Cov.: 32 AF XY: 0.374 AC XY: 27824 AN XY: 74310

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.375

Alfa AF: 0.221 Hom.: 436

Bravo AF: 0.381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.60

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: rs223331; hg19: chr4-103793565;