chr12-56021563-C-T

Variant names:

• chr12-56021563-C-T
• rs764681400
• NM_022465.4:c.70C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001351092.2(IKZF4):​c.-143C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000278 in 1,606,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: IKZF4 NM_001351092.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027832478).
• BS2: High AC in GnomAd4 at 54 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351092.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF4	NM_022465.4	MANE Select	c.70C>T	p.Arg24Trp	missense	Exon 1 of 8	NP_071910.3
	IKZF4	NM_001351092.2		c.-143C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001338021.1
	IKZF4	NM_001351089.2		c.70C>T	p.Arg24Trp	missense	Exon 5 of 12	NP_001338018.1	Q9H2S9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF4	ENST00000547167.6	TSL:1 MANE Select	c.70C>T	p.Arg24Trp	missense	Exon 1 of 8	ENSP00000448419.1	Q9H2S9-1
	IKZF4	ENST00000431367.6	TSL:1	c.70C>T	p.Arg24Trp	missense	Exon 2 of 9	ENSP00000412101.3	Q9H2S9-1
	IKZF4	ENST00000547791.2	TSL:1	c.46+113C>T		intron	N/A	ENSP00000450020.1	F8VPL6

Frequencies

GnomAD3 genomes AF: 0.000356 AC: 54 AN: 151732 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000253 AC: 59 AN: 233450 AF XY: 0.000237

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00247

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.000565

Gnomad NFE exome AF: 0.000189

Gnomad OTH exome AF: 0.000526

GnomAD4 exome AF: 0.000270 AC: 393 AN: 1454806 Hom.: 0 Cov.: 38 AF XY: 0.000275 AC XY: 199 AN XY: 722998

African (AFR) AF: 0.0000300 AC: 1 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 43658

Ashkenazi Jewish (ASJ) AF: 0.00258 AC: 67 AN: 25932

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39382

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84718

European-Finnish (FIN) AF: 0.000494 AC: 26 AN: 52666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000248 AC: 275 AN: 1109202

Other (OTH) AF: 0.000349 AC: 21 AN: 60102

GnomAD4 genome AF: 0.000356 AC: 54 AN: 151732 Hom.: 0 Cov.: 28 AF XY: 0.000500 AC XY: 37 AN XY: 74070

African (AFR) AF: 0.0000727 AC: 3 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00161 AC: 17 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67932

Other (OTH) AF: 0.000481 AC: 1 AN: 2078

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.000208

ExAC AF: 0.000116 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.94	P
Vest4		0.60
MVP		0.24
MPC		0.12
ClinPred		0.13	T
GERP RS		5.0
PromoterAI		-0.084	Neutral
Varity_R		0.13
gMVP		0.29
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs764681400; hg19: chr12-56415347; COSMIC: COSV56269550; COSMIC: COSV56269550;