rs6964823

Variant names:

• chr7-50392398-G-A
• rs6964823
• NM_006060.6:c.850+535G>A

Variant summary

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

The NM_006060.6(IKZF1):​c.850+535G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,110 control chromosomes in the GnomAD database, including 15,201 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 0.45 (15201 hom., cov: 30)
• Consequence: IKZF1 NM_006060.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 24 publications found

Genes affected

IKZF1 (HGNC:13176): (IKAROS family zinc finger 1) This gene encodes a transcription factor that belongs to the family of zinc-finger DNA-binding proteins associated with chromatin remodeling. The expression of this protein is restricted to the fetal and adult hemo-lymphopoietic system, and it functions as a regulator of lymphocyte differentiation. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. Most isoforms share a common C-terminal domain, which contains two zinc finger motifs that are required for hetero- or homo-dimerization, and for interactions with other proteins. The isoforms, however, differ in the number of N-terminal zinc finger motifs that bind DNA and in nuclear localization signal presence, resulting in members with and without DNA-binding properties. Only a few isoforms contain the requisite three or more N-terminal zinc motifs that confer high affinity binding to a specific core DNA sequence element in the promoters of target genes. The non-DNA-binding isoforms are largely found in the cytoplasm, and are thought to function as dominant-negative factors. Overexpression of some dominant-negative isoforms have been associated with B-cell malignancies, such as acute lymphoblastic leukemia (ALL). [provided by RefSeq, May 2014]

IKZF1 Gene-Disease associations (from GenCC):

• pancytopenia due to IKZF1 mutations

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• autoimmune disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000285165 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF1	NM_006060.6	c.850+535G>A		intron_variant	Intron 7 of 7	ENST00000331340.8	NP_006051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF1	ENST00000331340.8	c.850+535G>A		intron_variant	Intron 7 of 7	1	NM_006060.6	ENSP00000331614.3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67442 AN: 151004 Hom.: 15192 Cov.: 30

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.446 AC: 67467 AN: 151110 Hom.: 15201 Cov.: 30 AF XY: 0.437 AC XY: 32232 AN XY: 73806

African (AFR) AF: 0.435 AC: 17912 AN: 41214

American (AMR) AF: 0.390 AC: 5955 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1827 AN: 3440

East Asian (EAS) AF: 0.167 AC: 864 AN: 5170

South Asian (SAS) AF: 0.359 AC: 1710 AN: 4768

European-Finnish (FIN) AF: 0.399 AC: 4126 AN: 10334

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.496 AC: 33564 AN: 67638

Other (OTH) AF: 0.458 AC: 961 AN: 2096

Alfa AF: 0.481 Hom.: 29254

Bravo AF: 0.446

Asia WGS AF: 0.316 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.11
PhyloP100		-2.5

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: rs6964823; hg19: chr7-50460096;