rs2060941

Positions:

• chr17-39826630-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012481.5(IKZF3):​c.163+2757C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,240 control chromosomes in the GnomAD database, including 1,091 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 0.10 (1091 hom., cov: 32)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.163+2757C>A		intron_variant		ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.163+2757C>A		intron_variant		1	NM_012481.5	ENSP00000344544	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15979 AN: 152122 Hom.: 1090 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.105 AC: 15982 AN: 152240 Hom.: 1091 Cov.: 32 AF XY: 0.108 AC XY: 8010 AN XY: 74426

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.127 Hom.: 1709

Bravo AF: 0.0937

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.66

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: rs2060941; hg19: chr17-37982883;