chr17-39820216-C-T

Variant names:

• chr17-39820216-C-T
• rs9303277
• NM_012481.5:c.163+9171G>A

Variant summary

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

The NM_012481.5(IKZF3):​c.163+9171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,980 control chromosomes in the GnomAD database, including 20,565 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 0.52 (20565 hom., cov: 32)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 142 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.163+9171G>A		intron_variant	Intron 3 of 7	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.163+9171G>A		intron_variant	Intron 3 of 7	1	NM_012481.5	ENSP00000344544.3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78263 AN: 151860 Hom.: 20519 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.516 AC: 78371 AN: 151980 Hom.: 20565 Cov.: 32 AF XY: 0.515 AC XY: 38242 AN XY: 74270

African (AFR) AF: 0.596 AC: 24690 AN: 41438

American (AMR) AF: 0.439 AC: 6695 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1526 AN: 5170

South Asian (SAS) AF: 0.399 AC: 1926 AN: 4828

European-Finnish (FIN) AF: 0.583 AC: 6153 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33858 AN: 67942

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

Alfa AF: 0.498 Hom.: 88271

Bravo AF: 0.503

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.41
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: rs9303277; hg19: chr17-37976469;