rs907091

Variant names:

• chr17-39765489-C-T
• rs907091
• NM_012481.5:c.*301G>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.*301G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 268,528 control chromosomes in the GnomAD database, including 33,726 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 0.47 (17517 hom., cov: 32)
  • Exomes 𝑓: 0.52 (16209 hom.)
• Consequence: IKZF3 NM_012481.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 74 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	NM_012481.5	MANE Select	c.*301G>A		3_prime_UTR	Exon 8 of 8	NP_036613.2
	IKZF3	NM_001257408.2		c.*301G>A		3_prime_UTR	Exon 7 of 7	NP_001244337.1
	IKZF3	NM_183229.3		c.*301G>A		3_prime_UTR	Exon 7 of 7	NP_899052.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	ENST00000346872.8	TSL:1 MANE Select	c.*301G>A		3_prime_UTR	Exon 8 of 8	ENSP00000344544.3
	IKZF3	ENST00000535189.5	TSL:1	c.*301G>A		3_prime_UTR	Exon 7 of 7	ENSP00000438972.1
	IKZF3	ENST00000439167.6	TSL:1	c.*301G>A		3_prime_UTR	Exon 6 of 6	ENSP00000403776.2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71757 AN: 151806 Hom.: 17525 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.517 AC: 60249 AN: 116604 Hom.: 16209 Cov.: 0 AF XY: 0.524 AC XY: 31510 AN XY: 60118

African (AFR) AF: 0.342 AC: 1424 AN: 4164

American (AMR) AF: 0.586 AC: 3208 AN: 5476

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 2123 AN: 4102

East Asian (EAS) AF: 0.689 AC: 6260 AN: 9082

South Asian (SAS) AF: 0.610 AC: 4643 AN: 7606

European-Finnish (FIN) AF: 0.428 AC: 2441 AN: 5706

Middle Eastern (MID) AF: 0.532 AC: 316 AN: 594

European-Non Finnish (NFE) AF: 0.498 AC: 36185 AN: 72716

Other (OTH) AF: 0.510 AC: 3649 AN: 7158

GnomAD4 genome AF: 0.472 AC: 71753 AN: 151924 Hom.: 17517 Cov.: 32 AF XY: 0.473 AC XY: 35156 AN XY: 74268

African (AFR) AF: 0.353 AC: 14639 AN: 41416

American (AMR) AF: 0.560 AC: 8553 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1785 AN: 3464

East Asian (EAS) AF: 0.706 AC: 3654 AN: 5174

South Asian (SAS) AF: 0.601 AC: 2891 AN: 4808

European-Finnish (FIN) AF: 0.419 AC: 4413 AN: 10534

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34283 AN: 67950

Other (OTH) AF: 0.509 AC: 1074 AN: 2110

Alfa AF: 0.501 Hom.: 25609

Bravo AF: 0.482

Asia WGS AF: 0.567 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.0090
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: rs907091; hg19: chr17-37921742;