17-39798198-G-C

Position:

• chr17-39798198-G-C

Variant summary

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

The NM_012481.5(IKZF3):​c.164-5265C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,002 control chromosomes in the GnomAD database, including 1,309 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 0.092 (1309 hom., cov: 31)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF3	NM_012481.5	c.164-5265C>G		intron_variant		ENST00000346872.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF3	ENST00000346872.8	c.164-5265C>G		intron_variant		1	NM_012481.5	P1

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13942 AN: 151884 Hom.: 1294 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00991

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0921 AC: 13992 AN: 152002 Hom.: 1309 Cov.: 31 AF XY: 0.0901 AC XY: 6693 AN XY: 74296

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0752 Hom.: 109

Bravo AF: 0.0979

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.35

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: rs13313561; hg19: chr17-37954451;