12-56034603-C-T

Variant names:

• chr12-56034603-C-T
• rs369283900
• NM_022465.4:c.1030C>T

Variant summary

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

The NM_022465.4(IKZF4):​c.1030C>T​(p.Leu344Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L344P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: IKZF4 NM_022465.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06381887).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.1030C>T	p.Leu344Phe	missense	Exon 8 of 8	NP_071910.3
	IKZF4	NM_001351089.2		c.1030C>T	p.Leu344Phe	missense	Exon 12 of 12	NP_001338018.1	Q9H2S9-1
	IKZF4	NM_001351090.1		c.895C>T	p.Leu299Phe	missense	Exon 7 of 7	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.1030C>T	p.Leu344Phe	missense	Exon 8 of 8	ENSP00000448419.1	Q9H2S9-1
	IKZF4	ENST00000431367.6	TSL:1	c.1030C>T	p.Leu344Phe	missense	Exon 9 of 9	ENSP00000412101.3	Q9H2S9-1
	IKZF4	ENST00000547791.2	TSL:1	c.895C>T	p.Leu299Phe	missense	Exon 7 of 7	ENSP00000450020.1	F8VPL6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460696 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726546

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111274

Other (OTH) AF: 0.00 AC: 0 AN: 60306

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.063
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.27
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.053
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.14	T
Polyphen		0.077	B
Vest4		0.12
MutPred		0.47		Loss of stability (P = 0.149)
MVP		0.22
MPC		1.3
ClinPred		0.85	D
GERP RS		4.0
Varity_R		0.12
gMVP		0.21
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs369283900; hg19: chr12-56428387;