chr6-109467739-AAAAAAC-A
Position:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1
The NM_014797.3(ZBTB24):c.1289-11_1289-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,613,460 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 1 hom. )
Consequence
ZBTB24
NM_014797.3 splice_region, splice_polypyrimidine_tract, intron
NM_014797.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.47
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 6-109467739-AAAAAAC-A is Benign according to our data. Variant chr6-109467739-AAAAAAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 539541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000125 (19/152330) while in subpopulation EAS AF= 0.00193 (10/5182). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZBTB24 | NM_014797.3 | c.1289-11_1289-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000230122.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZBTB24 | ENST00000230122.4 | c.1289-11_1289-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014797.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152212Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
19
AN:
152212
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000840 AC: 21AN: 250056Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 135208
GnomAD3 exomes
AF:
AC:
21
AN:
250056
Hom.:
AF XY:
AC XY:
14
AN XY:
135208
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461130Hom.: 1 AF XY: 0.0000688 AC XY: 50AN XY: 726808
GnomAD4 exome
AF:
AC:
115
AN:
1461130
Hom.:
AF XY:
AC XY:
50
AN XY:
726808
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000125 AC: 19AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74490
GnomAD4 genome
AF:
AC:
19
AN:
152330
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
74490
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency-centromeric instability-facial anomalies syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
ZBTB24-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at