chr7-50403915-G-A

Variant names:

• chr7-50403915-G-A
• rs11980407
• NM_006060.6:c.*3288G>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.*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
• Publications: 18 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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006060.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF1	NM_006060.6	MANE Select	c.*3288G>A		3_prime_UTR	Exon 8 of 8	NP_006051.1
	IKZF1	NM_001410879.1		c.*3288G>A		3_prime_UTR	Exon 9 of 9	NP_001397808.1
	IKZF1	NM_001220765.3		c.*3288G>A		3_prime_UTR	Exon 7 of 7	NP_001207694.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF1	ENST00000331340.8	TSL:1 MANE Select	c.*3288G>A		3_prime_UTR	Exon 8 of 8	ENSP00000331614.3
	IKZF1	ENST00000698575.1		c.*3288G>A		3_prime_UTR	Exon 5 of 5	ENSP00000513806.1
	IKZF1	ENST00000615491.4	TSL:5	c.*3288G>A		3_prime_UTR	Exon 5 of 5	ENSP00000478368.1

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

African (AFR) AF: 0.211 AC: 612 AN: 2906

American (AMR) AF: 0.238 AC: 447 AN: 1878

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 873 AN: 3974

East Asian (EAS) AF: 0.0866 AC: 817 AN: 9438

South Asian (SAS) AF: 0.276 AC: 149 AN: 540

European-Finnish (FIN) AF: 0.339 AC: 160 AN: 472

Middle Eastern (MID) AF: 0.269 AC: 106 AN: 394

European-Non Finnish (NFE) AF: 0.269 AC: 10528 AN: 39178

Other (OTH) AF: 0.238 AC: 1273 AN: 5338

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

African (AFR) AF: 0.194 AC: 8044 AN: 41454

American (AMR) AF: 0.242 AC: 3696 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3470

East Asian (EAS) AF: 0.105 AC: 544 AN: 5188

South Asian (SAS) AF: 0.289 AC: 1395 AN: 4822

European-Finnish (FIN) AF: 0.328 AC: 3467 AN: 10576

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18487 AN: 67988

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.258 Hom.: 2377

Bravo AF: 0.237

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.68
DANN	Benign	0.58
PhyloP100		-0.011

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: rs11980407; hg19: chr7-50471613;