12-56023144-A-C

Variant names:

• chr12-56023144-A-C
• rs2456973
• NM_022465.4:c.88-527A>C

Variant summary

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

The NM_022465.4(IKZF4):​c.88-527A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,044 control chromosomes in the GnomAD database, including 5,553 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 0.26 (5553 hom., cov: 31)
• Consequence: IKZF4 NM_022465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 71 publications found

Genes affected

IKZF4 (HGNC:13179): (IKAROS family zinc finger 4) Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Eos, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]

ENSG00000257449 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022465.4. 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
	IKZF4	NM_022465.4	MANE Select	c.88-527A>C		intron	N/A	NP_071910.3
	IKZF4	NM_001351089.2		c.88-527A>C		intron	N/A	NP_001338018.1
	IKZF4	NM_001351090.1		c.46+1694A>C		intron	N/A	NP_001338019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF4	ENST00000547167.6	TSL:1 MANE Select	c.88-527A>C		intron	N/A	ENSP00000448419.1
	IKZF4	ENST00000431367.6	TSL:1	c.88-527A>C		intron	N/A	ENSP00000412101.3
	IKZF4	ENST00000547791.2	TSL:1	c.46+1694A>C		intron	N/A	ENSP00000450020.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38880 AN: 151928 Hom.: 5552 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.256 AC: 38877 AN: 152044 Hom.: 5553 Cov.: 31 AF XY: 0.252 AC XY: 18746 AN XY: 74342

African (AFR) AF: 0.133 AC: 5522 AN: 41500

American (AMR) AF: 0.225 AC: 3442 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5162

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4820

European-Finnish (FIN) AF: 0.300 AC: 3172 AN: 10572

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.328 AC: 22257 AN: 67942

Other (OTH) AF: 0.271 AC: 573 AN: 2112

Alfa AF: 0.296 Hom.: 15921

Bravo AF: 0.247

Asia WGS AF: 0.181 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.3
DANN	Benign	0.52
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs2456973; hg19: chr12-56416928;