rs9909593

chr17-39813896-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012481.5(IKZF3):c.163+15491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,122 control chromosomes in the GnomAD database, including 12,176 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 0.38 (12176 hom., cov: 31)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

Genes affected

IKZF3 (HGNC:13178): (IKAROS family zinc finger 3) This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this protein family (Ikaros, Aiolos and Helios) are hematopoietic-specific transcription factors involved in the regulation of lymphocyte development. This gene product is a transcription factor that is important in the regulation of B lymphocyte proliferation and differentiation. Both Ikaros and Aiolos can participate in chromatin remodeling. Regulation of gene expression in B lymphocytes by Aiolos is complex as it appears to require the sequential formation of Ikaros homodimers, Ikaros/Aiolos heterodimers, and Aiolos homodimers. Several alternative transcripts encoding different isoforms have been described, as well as some non-protein coding variants. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF3	NM_012481.5	c.163+15491T>C		intron_variant		ENST00000346872.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF3	ENST00000346872.8	c.163+15491T>C		intron_variant		1	NM_012481.5	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57861 AN: 152002 Hom.: 12170 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.380 AC: 57879 AN: 152122 Hom.: 12176 Cov.: 31 AF XY: 0.384 AC XY: 28538 AN XY: 74358

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.375

Alfa AF: 0.382 Hom.: 3190

Bravo AF: 0.355

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	16
Dann	Benign	0.52

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: rs9909593; hg19: chr17-37970149;