12-56018703-T-G

Variant names:

• chr12-56018703-T-G
• rs1701704
• NM_001351089.2:c.-162+526T>G

Variant summary

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

The NM_001351089.2(IKZF4):​c.-162+526T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 150,928 control chromosomes in the GnomAD database, including 5,395 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 (5395 hom., cov: 30)
• Consequence: IKZF4 NM_001351089.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 139 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=-0.78).
• 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_001351089.2. 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_001351089.2		c.-162+526T>G		intron	N/A	NP_001338018.1
	IKZF4	NM_001351091.2		c.40+526T>G		intron	N/A	NP_001338020.1
	LOC105369781	NR_135023.1		n.63+6326A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF4	ENST00000262032.9	TSL:5	c.-162+526T>G		intron	N/A	ENSP00000262032.5
	IKZF4	ENST00000552689.1	TSL:3	c.-159+526T>G		intron	N/A	ENSP00000449168.1
	IKZF4	ENST00000548601.5	TSL:3	n.118+526T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.251 AC: 37834 AN: 150808 Hom.: 5394 Cov.: 30

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.251 AC: 37833 AN: 150928 Hom.: 5395 Cov.: 30 AF XY: 0.247 AC XY: 18158 AN XY: 73578

African (AFR) AF: 0.117 AC: 4814 AN: 41138

American (AMR) AF: 0.223 AC: 3349 AN: 15036

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1151 AN: 3460

East Asian (EAS) AF: 0.211 AC: 1084 AN: 5148

South Asian (SAS) AF: 0.236 AC: 1120 AN: 4750

European-Finnish (FIN) AF: 0.298 AC: 3081 AN: 10352

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22171 AN: 67774

Other (OTH) AF: 0.264 AC: 545 AN: 2068

Alfa AF: 0.302 Hom.: 33764

Bravo AF: 0.242

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.82
PhyloP100		0.58
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: rs1701704; hg19: chr12-56412487;