rs13313561

Variant names:

• chr17-39798198-G-C
• rs13313561
• NM_012481.5:c.164-5265C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	NM_012481.5	MANE Select	c.164-5265C>G		intron	N/A	NP_036613.2
	IKZF3	NM_001257408.2		c.62-5265C>G		intron	N/A	NP_001244337.1
	IKZF3	NM_183229.3		c.164-5265C>G		intron	N/A	NP_899052.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	ENST00000346872.8	TSL:1 MANE Select	c.164-5265C>G		intron	N/A	ENSP00000344544.3
	IKZF3	ENST00000535189.5	TSL:1	c.62-5265C>G		intron	N/A	ENSP00000438972.1
	IKZF3	ENST00000439167.6	TSL:1	c.62-5265C>G		intron	N/A	ENSP00000403776.2

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

African (AFR) AF: 0.244 AC: 10102 AN: 41406

American (AMR) AF: 0.0424 AC: 648 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4820

European-Finnish (FIN) AF: 0.0392 AC: 414 AN: 10572

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0373 AC: 2533 AN: 67982

Other (OTH) AF: 0.0749 AC: 158 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.35
PhyloP100		-0.67
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: rs13313561; hg19: chr17-37954451;