rs11980407

Positions:

• chr7-50403915-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006060.6(IKZF1):​c.*3288G>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 0.242 in 216,228 control chromosomes in the GnomAD database, including 6,715 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 0.25 (4792 hom., cov: 33)
  • Exomes 𝑓: 0.23 (1923 hom.)
• Consequence: IKZF1 NM_006060.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKZF1	NM_006060.6	c.*3288G>A		3_prime_UTR_variant	8/8	ENST00000331340.8	NP_006051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF1	ENST00000331340.8	c.*3288G>A		3_prime_UTR_variant	8/8	1	NM_006060.6	ENSP00000331614	A1
IKZF1	ENST00000346667.8	c.*3288G>A		3_prime_UTR_variant	3/3	5		ENSP00000340080
IKZF1	ENST00000615491.4	c.*3288G>A		3_prime_UTR_variant	5/5	5		ENSP00000478368
IKZF1	ENST00000698575.1	c.*3288G>A		3_prime_UTR_variant	5/5			ENSP00000513806

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37255 AN: 151992 Hom.: 4788 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.233 AC: 14965 AN: 64118 Hom.: 1923 Cov.: 0 AF XY: 0.233 AC XY: 6935 AN XY: 29780

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.0866

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.245 AC: 37279 AN: 152110 Hom.: 4792 Cov.: 33 AF XY: 0.248 AC XY: 18460 AN XY: 74362

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.250

Alfa AF: 0.259 Hom.: 2007

Bravo AF: 0.237

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.68
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs11980407; hg19: chr7-50471613;