10-123006341-T-C

Variant names:

• chr10-123006341-T-C
• rs9328842
• NM_001372123.1:c.-47+685A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372123.1(IKZF5):​c.-47+685A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,984 control chromosomes in the GnomAD database, including 27,191 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 0.58 (27191 hom., cov: 32)
• Consequence: IKZF5 NM_001372123.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• Publications: 2 publications found

Genes affected

IKZF5 (HGNC:14283): (IKAROS family zinc finger 5) Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Pegasus, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]

IKZF5 Gene-Disease associations (from GenCC):

• thrombocytopenia 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF5	NM_001372123.1	c.-47+685A>G		intron_variant	Intron 2 of 4	ENST00000368886.10	NP_001359052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF5	ENST00000368886.10	c.-47+685A>G		intron_variant	Intron 2 of 4	1	NM_001372123.1	ENSP00000357881.5

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88732 AN: 151868 Hom.: 27182 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.584 AC: 88779 AN: 151984 Hom.: 27191 Cov.: 32 AF XY: 0.579 AC XY: 43003 AN XY: 74288

African (AFR) AF: 0.453 AC: 18772 AN: 41442

American (AMR) AF: 0.529 AC: 8072 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2464 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1301 AN: 5172

South Asian (SAS) AF: 0.432 AC: 2080 AN: 4816

European-Finnish (FIN) AF: 0.654 AC: 6903 AN: 10552

Middle Eastern (MID) AF: 0.648 AC: 188 AN: 290

European-Non Finnish (NFE) AF: 0.693 AC: 47080 AN: 67952

Other (OTH) AF: 0.609 AC: 1287 AN: 2112

Alfa AF: 0.646 Hom.: 17525

Bravo AF: 0.568

Asia WGS AF: 0.342 AC: 1191 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.63
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs9328842; hg19: chr10-124765857;