rs9909593

Variant names:

• chr17-39813896-A-G
• rs9909593
• NM_012481.5:c.163+15491T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 publications found

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]

IKZF3 Gene-Disease associations (from GenCC):

• immunodeficiency 84

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.163+15491T>C		intron_variant	Intron 3 of 7	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.163+15491T>C		intron_variant	Intron 3 of 7	1	NM_012481.5	ENSP00000344544.3

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

African (AFR) AF: 0.206 AC: 8551 AN: 41522

American (AMR) AF: 0.378 AC: 5774 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1714 AN: 3464

East Asian (EAS) AF: 0.294 AC: 1522 AN: 5172

South Asian (SAS) AF: 0.382 AC: 1844 AN: 4824

European-Finnish (FIN) AF: 0.544 AC: 5744 AN: 10566

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31212 AN: 67966

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.369 Hom.: 5123

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
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9909593; hg19: chr17-37970149;