4-102872502-T-C

Position:

• chr4-102872502-T-C

Variant summary

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

The NM_001008388.5(CISD2):​c.103+3315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,016 control chromosomes in the GnomAD database, including 26,464 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 0.58 (26464 hom., cov: 32)
• Consequence: CISD2 NM_001008388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CISD2	NM_001008388.5	c.103+3315T>C		intron_variant		ENST00000273986.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CISD2	ENST00000273986.10	c.103+3315T>C		intron_variant		1	NM_001008388.5	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87381 AN: 151896 Hom.: 26415 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.576 AC: 87486 AN: 152016 Hom.: 26464 Cov.: 32 AF XY: 0.575 AC XY: 42721 AN XY: 74316

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.578

Alfa AF: 0.525 Hom.: 2533

Bravo AF: 0.593

Asia WGS AF: 0.527 AC: 1830 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.3
DANN	Benign	0.57

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: rs223330; hg19: chr4-103793659;