12-56009793-C-T

Position:

• chr12-56009793-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047429349.1(IKZF4):​c.-1714C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,004 control chromosomes in the GnomAD database, including 5,430 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 (5430 hom., cov: 31)
• Consequence: IKZF4 XM_047429349.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKZF4	XM_047429349.1	c.-1714C>T		5_prime_UTR_variant	1/8		XP_047285305.1
IKZF4	NM_001351089.2	c.-291-1624C>T		intron_variant			NP_001338018.1
IKZF4	NM_001351091.2	c.-90-1624C>T		intron_variant			NP_001338020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF4	ENST00000262032.9	c.-291-1624C>T		intron_variant		5		ENSP00000262032	P1
IKZF4	ENST00000548601.5	n.66+2059C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38070 AN: 151888 Hom.: 5429 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.250 AC: 38070 AN: 152004 Hom.: 5430 Cov.: 31 AF XY: 0.247 AC XY: 18354 AN XY: 74296

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.268

Alfa AF: 0.306 Hom.: 7405

Bravo AF: 0.241

Asia WGS AF: 0.180 AC: 627 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	17
DANN	Benign	0.41

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: rs772921; hg19: chr12-56403577;