17-39765489-C-T

Position:

• chr17-39765489-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.*301G>A		3_prime_UTR_variant	8/8	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.*301G>A		3_prime_UTR_variant	8/8	1	NM_012481.5	ENSP00000344544	P1

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

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.689

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.510

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

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.509

Alfa AF: 0.505 Hom.: 20033

Bravo AF: 0.482

Asia WGS AF: 0.567 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.63

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: rs907091; hg19: chr17-37921742;