dbSNP rs62447207: IKZF1:c.*1813G>T (chr7-50402440-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006060.6(IKZF1):c.*1813G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 231,050 control chromosomes in the GnomAD database, including 3,258 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 0.15 ( 2017 hom., cov: 33)

Exomes 𝑓: 0.16 ( 1241 hom. )

Consequence

IKZF1
NM_006060.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Variant links:

Genes affected

IKZF1 (HGNC:13176): (IKAROS family zinc finger 1) This gene encodes a transcription factor that belongs to the family of zinc-finger DNA-binding proteins associated with chromatin remodeling. The expression of this protein is restricted to the fetal and adult hemo-lymphopoietic system, and it functions as a regulator of lymphocyte differentiation. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. Most isoforms share a common C-terminal domain, which contains two zinc finger motifs that are required for hetero- or homo-dimerization, and for interactions with other proteins. The isoforms, however, differ in the number of N-terminal zinc finger motifs that bind DNA and in nuclear localization signal presence, resulting in members with and without DNA-binding properties. Only a few isoforms contain the requisite three or more N-terminal zinc motifs that confer high affinity binding to a specific core DNA sequence element in the promoters of target genes. The non-DNA-binding isoforms are largely found in the cytoplasm, and are thought to function as dominant-negative factors. Overexpression of some dominant-negative isoforms have been associated with B-cell malignancies, such as acute lymphoblastic leukemia (ALL). [provided by RefSeq, May 2014]

IKZF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF1	NM_006060.6 link	c.*1813G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000331340.8	NP_006051.1	Q13422-1R9R4D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF1	ENST00000331340.8 link	c.*1813G>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_006060.6	ENSP00000331614.3		Q13422-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22962

AN:

151984

Hom.:

2019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.0374

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.175

GnomAD4 exome

AF:

0.161

AC:

12745

AN:

78948

Hom.:

1241

Cov.:

AF XY:

0.164

AC XY:

5950

AN XY:

36328

show subpopulations

Gnomad4 AFR exome

AF:

0.0794

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.0204

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.151

AC:

22968

AN:

152102

Hom.:

2017

Cov.:

AF XY:

0.151

AC XY:

11217

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.0373

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.174

Hom.:

289

Bravo

AF:

0.150

Asia WGS

AF:

0.110

AC:

382

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

4.3

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over