12-56018703-T-G

Variant names:

• chr12-56018703-T-G
• rs1701704
• NM_001351089.2:c.-162+526T>G

Variant summary

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

The NM_001351089.2(IKZF4):​c.-162+526T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 150,928 control chromosomes in the GnomAD database, including 5,395 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 (5395 hom., cov: 30)
• Consequence: IKZF4 NM_001351089.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

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]

LOC105369781 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF4	NM_001351089.2	c.-162+526T>G		intron_variant	Intron 3 of 11		NP_001338018.1
IKZF4	NM_001351091.2	c.40+526T>G		intron_variant	Intron 3 of 8		NP_001338020.1
IKZF4	XM_017019806.2	c.-162+526T>G		intron_variant	Intron 3 of 11		XP_016875295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF4	ENST00000262032.9	c.-162+526T>G		intron_variant	Intron 3 of 11	5		ENSP00000262032.5
IKZF4	ENST00000552689.1	c.-159+526T>G		intron_variant	Intron 2 of 3	3		ENSP00000449168.1
IKZF4	ENST00000548601.5	n.118+526T>G		intron_variant	Intron 2 of 5	3
IKZF4	ENST00000550860.5	n.414+526T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 37834 AN: 150808 Hom.: 5394 Cov.: 30

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.251 AC: 37833 AN: 150928 Hom.: 5395 Cov.: 30 AF XY: 0.247 AC XY: 18158 AN XY: 73578

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.264

Alfa AF: 0.311 Hom.: 17485

Bravo AF: 0.242

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.82

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: rs1701704; hg19: chr12-56412487;