rs2456973

chr12-56023144-A-Cchr12-56023144-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105369781 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF4	NM_022465.4	c.88-527A>C		intron_variant		ENST00000547167.6
LOC105369781	NR_135023.1	n.63+1885T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF4	ENST00000547167.6	c.88-527A>C		intron_variant		1	NM_022465.4	P1

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.271

Alfa AF: 0.267 Hom.: 2245

Bravo AF: 0.247

Asia WGS AF: 0.181 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.3
Dann	Benign	0.52

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: rs2456973; hg19: chr12-56416928;