rs10876864

Variant names:

• chr12-56007301-G-A
• rs10876864
• NM_001351089.2:c.-725G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-56007301-G-A
• chr12-56007301-G-T

Variant summary

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

The NM_001351089.2(IKZF4):​c.-725G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,830 control chromosomes in the GnomAD database, including 22,036 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 0.51 (22036 hom., cov: 29)
• Consequence: IKZF4 NM_001351089.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 133 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF4	NM_001351089.2	c.-725G>A		upstream_gene_variant			NP_001338018.1
IKZF4	NM_001351091.2	c.-524G>A		upstream_gene_variant			NP_001338020.1
IKZF4	XM_017019806.2	c.-968G>A		upstream_gene_variant			XP_016875295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76886 AN: 151714 Hom.: 22035 Cov.: 29

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.506 AC: 76896 AN: 151830 Hom.: 22036 Cov.: 29 AF XY: 0.516 AC XY: 38289 AN XY: 74170

African (AFR) AF: 0.220 AC: 9103 AN: 41404

American (AMR) AF: 0.651 AC: 9937 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3472

East Asian (EAS) AF: 0.780 AC: 3999 AN: 5130

South Asian (SAS) AF: 0.724 AC: 3484 AN: 4810

European-Finnish (FIN) AF: 0.602 AC: 6334 AN: 10520

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40250 AN: 67924

Other (OTH) AF: 0.560 AC: 1177 AN: 2100

Alfa AF: 0.566 Hom.: 82461

Bravo AF: 0.497

Asia WGS AF: 0.731 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.084
DANN	Benign	0.77
PhyloP100		-2.3
PromoterAI		-0.046	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10876864; hg19: chr12-56401085;