rs11552046
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_006060.6(IKZF1):c.*1734G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 230,132 control chromosomes in the GnomAD database, including 68 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 0.014 ( 65 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 3 hom. )
Consequence
IKZF1
NM_006060.6 3_prime_UTR
NM_006060.6 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0260
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2180/152182) while in subpopulation AFR AF= 0.0506 (2098/41492). AF 95% confidence interval is 0.0488. There are 65 homozygotes in gnomad4. There are 1046 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 2174 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IKZF1 | NM_006060.6 | c.*1734G>A | 3_prime_UTR_variant | 8/8 | ENST00000331340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKZF1 | ENST00000331340.8 | c.*1734G>A | 3_prime_UTR_variant | 8/8 | 1 | NM_006060.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0143 AC: 2174AN: 152064Hom.: 65 Cov.: 33
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GnomAD4 exome AF: 0.00277 AC: 216AN: 77950Hom.: 3 Cov.: 0 AF XY: 0.00223 AC XY: 80AN XY: 35940
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GnomAD4 genome ? AF: 0.0143 AC: 2180AN: 152182Hom.: 65 Cov.: 33 AF XY: 0.0141 AC XY: 1046AN XY: 74422
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at