17-39851068-T-G

Variant names:

• chr17-39851068-T-G
• rs35222145
• NM_012481.5:c.7+13052A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012481.5(IKZF3):​c.7+13052A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 147,186 control chromosomes in the GnomAD database, including 14,259 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 0.44 (14259 hom., cov: 26)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.7+13052A>C		intron_variant	Intron 1 of 7	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.7+13052A>C		intron_variant	Intron 1 of 7	1	NM_012481.5	ENSP00000344544.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 64286 AN: 147166 Hom.: 14239 Cov.: 26

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.437 AC: 64325 AN: 147186 Hom.: 14259 Cov.: 26 AF XY: 0.435 AC XY: 31090 AN XY: 71430

African (AFR) AF: 0.403 AC: 16146 AN: 40038

American (AMR) AF: 0.411 AC: 5904 AN: 14354

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1515 AN: 3436

East Asian (EAS) AF: 0.265 AC: 1347 AN: 5092

South Asian (SAS) AF: 0.370 AC: 1752 AN: 4740

European-Finnish (FIN) AF: 0.508 AC: 4733 AN: 9314

Middle Eastern (MID) AF: 0.351 AC: 99 AN: 282

European-Non Finnish (NFE) AF: 0.468 AC: 31422 AN: 67076

Other (OTH) AF: 0.418 AC: 825 AN: 1976

Alfa AF: 0.301 Hom.: 752

Bravo AF: 0.425

Asia WGS AF: 0.379 AC: 1312 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.091
PhyloP100		-2.5
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: rs35222145; hg19: chr17-38007321;