rs2232449

chr6-109466244-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014797.3(ZBTB24):c.1701C>T(p.Pro567=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,614,176 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (101 hom., cov: 32)
  • Exomes 𝑓: 0.016 (288 hom.)
• Consequence: ZBTB24 NM_014797.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.34

Genes affected

ZBTB24 (HGNC:21143): (zinc finger and BTB domain containing 24) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in nucleus. Implicated in immunodeficiency-centromeric instability-facial anomalies syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-109466244-G-A is Benign according to our data. Variant chr6-109466244-G-A is described in ClinVar as [Benign]. Clinvar id is 472202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB24	NM_014797.3	c.1701C>T	p.Pro567=	synonymous_variant	7/7	ENST00000230122.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB24	ENST00000230122.4	c.1701C>T	p.Pro567=	synonymous_variant	7/7	1	NM_014797.3	P1

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4240 AN: 152168 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.00632

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0162 AC: 4062 AN: 250802 Hom.: 69 AF XY: 0.0160 AC XY: 2164 AN XY: 135528

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00862

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0189

Gnomad FIN exome AF: 0.00693

Gnomad NFE exome AF: 0.0154

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.0162 AC: 23624 AN: 1461890 Hom.: 288 Cov.: 33 AF XY: 0.0160 AC XY: 11609 AN XY: 727248

Gnomad4 AFR exome AF: 0.0649

Gnomad4 AMR exome AF: 0.00879

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0190

Gnomad4 FIN exome AF: 0.00786

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0279 AC: 4242 AN: 152286 Hom.: 101 Cov.: 32 AF XY: 0.0268 AC XY: 1996 AN XY: 74478

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.00632

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0235 Hom.: 43

Bravo AF: 0.0299

Asia WGS AF: 0.0140 AC: 47 AN: 3478

EpiCase AF: 0.0152

EpiControl AF: 0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 23, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.7
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2232449; hg19: chr6-109787447; COSMIC: COSV57781994; COSMIC: COSV57781994;