17-39816455-G-T

Variant names:

• chr17-39816455-G-T
• rs12450323
• NM_012481.5:c.163+12932C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012481.5(IKZF3):​c.163+12932C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,062 control chromosomes in the GnomAD database, including 4,112 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 0.19 (4112 hom., cov: 32)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012481.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	NM_012481.5	MANE Select	c.163+12932C>A		intron	N/A	NP_036613.2
	IKZF3	NM_001257408.2		c.61+15643C>A		intron	N/A	NP_001244337.1
	IKZF3	NM_183229.3		c.163+12932C>A		intron	N/A	NP_899052.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	ENST00000346872.8	TSL:1 MANE Select	c.163+12932C>A		intron	N/A	ENSP00000344544.3
	IKZF3	ENST00000535189.5	TSL:1	c.61+15643C>A		intron	N/A	ENSP00000438972.1
	IKZF3	ENST00000439167.6	TSL:1	c.61+15643C>A		intron	N/A	ENSP00000403776.2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29110 AN: 151944 Hom.: 4113 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.191 AC: 29098 AN: 152062 Hom.: 4112 Cov.: 32 AF XY: 0.198 AC XY: 14680 AN XY: 74312

African (AFR) AF: 0.0447 AC: 1855 AN: 41482

American (AMR) AF: 0.335 AC: 5120 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3344 AN: 5160

South Asian (SAS) AF: 0.238 AC: 1145 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2402 AN: 10568

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13955 AN: 67966

Other (OTH) AF: 0.216 AC: 455 AN: 2110

Alfa AF: 0.110 Hom.: 175

Bravo AF: 0.203

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.16
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: rs12450323; hg19: chr17-37972708;