12-56023702-C-T

Variant names:

• chr12-56023702-C-T
• NM_022465.4:c.119C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022465.4(IKZF4):​c.119C>T​(p.Pro40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,618 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IKZF4 NM_022465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14536032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022465.4. 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.119C>T	p.Pro40Leu	missense	Exon 2 of 8	NP_071910.3
	IKZF4	NM_001351089.2		c.119C>T	p.Pro40Leu	missense	Exon 6 of 12	NP_001338018.1	Q9H2S9-1
	IKZF4	NM_001351090.1		c.47-1352C>T		intron	N/A	NP_001338019.1	F8VPL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF4	ENST00000547167.6	TSL:1 MANE Select	c.119C>T	p.Pro40Leu	missense	Exon 2 of 8	ENSP00000448419.1	Q9H2S9-1
	IKZF4	ENST00000431367.6	TSL:1	c.119C>T	p.Pro40Leu	missense	Exon 3 of 9	ENSP00000412101.3	Q9H2S9-1
	IKZF4	ENST00000547791.2	TSL:1	c.47-1352C>T		intron	N/A	ENSP00000450020.1	F8VPL6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461618 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111828

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

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	0.20
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.035	D
Polyphen		0.0	B
Vest4		0.30
MutPred		0.30		Loss of helix (P = 0.0237)
MVP		0.72
MPC		0.11
ClinPred		0.72	D
GERP RS		4.6
Varity_R		0.13
gMVP		0.22
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -31

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

Other links and lift over

hg19: chr12-56417486; COSMIC: COSV56270997; COSMIC: COSV56270997;