17-39773563-T-C

Variant names:

• chr17-39773563-T-C
• rs2313430
• NM_012481.5:c.826+4088A>G

Variant summary

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

The NM_012481.5(IKZF3):​c.826+4088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,054 control chromosomes in the GnomAD database, including 18,117 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 0.48 (18117 hom., cov: 32)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870

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=-0.64).
• 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 rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.826+4088A>G		intron_variant	Intron 7 of 7	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.826+4088A>G		intron_variant	Intron 7 of 7	1	NM_012481.5	ENSP00000344544.3

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73459 AN: 151936 Hom.: 18119 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.483 AC: 73474 AN: 152054 Hom.: 18117 Cov.: 32 AF XY: 0.484 AC XY: 35947 AN XY: 74300

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.519

Alfa AF: 0.500 Hom.: 2716

Bravo AF: 0.496

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.61

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: rs2313430; hg19: chr17-37929816;