Variant 17-39829548-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012481.5(IKZF3):c.62-60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,189,472 control chromosomes in the GnomAD database, including 166,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 22257 hom., cov: 33)

Exomes 𝑓: 0.52 ( 144388 hom. )

Consequence

IKZF3
NM_012481.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.853

Variant links:

Genes affected

IKZF3 (HGNC:13178): (IKAROS family zinc finger 3) This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this protein family (Ikaros, Aiolos and Helios) are hematopoietic-specific transcription factors involved in the regulation of lymphocyte development. This gene product is a transcription factor that is important in the regulation of B lymphocyte proliferation and differentiation. Both Ikaros and Aiolos can participate in chromatin remodeling. Regulation of gene expression in B lymphocytes by Aiolos is complex as it appears to require the sequential formation of Ikaros homodimers, Ikaros/Aiolos heterodimers, and Aiolos homodimers. Several alternative transcripts encoding different isoforms have been described, as well as some non-protein coding variants. [provided by RefSeq, Apr 2012]

IKZF3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-39829548-A-G is Benign according to our data. Variant chr17-39829548-A-G is described in ClinVar as [Benign]. Clinvar id is 2688020.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF3	NM_012481.5 linkuse as main transcript	c.62-60T>C		intron_variant		ENST00000346872.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF3	ENST00000346872.8 linkuse as main transcript	c.62-60T>C		intron_variant		1	NM_012481.5	P1	Q9UKT9-1

Frequencies

GnomAD3 genomes

AF:

0.536

AC:

81406

AN:

151990

Hom.:

22207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.501

GnomAD4 exome

AF:

0.523

AC:

542601

AN:

1037364

Hom.:

144388

AF XY:

0.519

AC XY:

276528

AN XY:

533192

show subpopulations

Gnomad4 AFR exome

AF:

0.638

Gnomad4 AMR exome

AF:

0.416

Gnomad4 ASJ exome

AF:

0.523

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.511

GnomAD4 genome

AF:

0.536

AC:

81517

AN:

152108

Hom.:

22257

Cov.:

AF XY:

0.534

AC XY:

39689

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.513

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.512

Hom.:

4164

Bravo

AF:

0.525

Asia WGS

AF:

0.434

AC:

1508

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied by a panel of primary immunodeficiencies. Number of patients: 66. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.9

DANN

Benign

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over