rs11978267

Variant names:

• chr7-50398606-A-G
• rs11978267
• NM_006060.6:c.851-1312A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-50398606-A-G
• chr7-50398606-A-C

Variant summary

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

The NM_006060.6(IKZF1):​c.851-1312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,166 control chromosomes in the GnomAD database, including 4,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

• Frequency: Genomes: 𝑓 0.25 (4903 hom., cov: 33)
• Consequence: IKZF1 NM_006060.6 intron
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.937
• Publications: 70 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: Illumina, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF1	NM_006060.6	MANE Select	c.851-1312A>G		intron	N/A	NP_006051.1	Q13422-1
	IKZF1	NM_001410879.1		c.911-1312A>G		intron	N/A	NP_001397808.1	A0A8V8TNQ0
	IKZF1	NM_001220765.3		c.725-1312A>G		intron	N/A	NP_001207694.1	Q13422-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF1	ENST00000331340.8	TSL:1 MANE Select	c.851-1312A>G		intron	N/A	ENSP00000331614.3	Q13422-1
	IKZF1	ENST00000359197.9	TSL:1	c.725-1312A>G		intron	N/A	ENSP00000352123.5	Q13422-7
	IKZF1	ENST00000439701.2	TSL:1	c.725-1312A>G		intron	N/A	ENSP00000413025.1	Q13422-7

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37677 AN: 152050 Hom.: 4899 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.248 AC: 37702 AN: 152166 Hom.: 4903 Cov.: 33 AF XY: 0.252 AC XY: 18720 AN XY: 74380

African (AFR) AF: 0.197 AC: 8178 AN: 41532

American (AMR) AF: 0.242 AC: 3697 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3466

East Asian (EAS) AF: 0.110 AC: 573 AN: 5188

South Asian (SAS) AF: 0.308 AC: 1485 AN: 4818

European-Finnish (FIN) AF: 0.336 AC: 3551 AN: 10580

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

European-Non Finnish (NFE) AF: 0.273 AC: 18578 AN: 67978

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.252 Hom.: 17472

Bravo AF: 0.239

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Leukemia, acute lymphocytic, susceptibility to, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.94
DANN	Benign	0.33
PhyloP100		-0.94

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: rs11978267; hg19: chr7-50466304;