rs6911838

Variant names:

• chr6-109478720-C-T
• rs6911838
• NM_014797.3:c.953-1790G>A

Variant summary

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

The NM_014797.3(ZBTB24):​c.953-1790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,528 control chromosomes in the GnomAD database, including 11,718 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 0.39 (11718 hom., cov: 30)
• Consequence: ZBTB24 NM_014797.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 10 publications found

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]

ZBTB24 Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB24	NM_014797.3	c.953-1790G>A		intron_variant	Intron 2 of 6	ENST00000230122.4	NP_055612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB24	ENST00000230122.4	c.953-1790G>A		intron_variant	Intron 2 of 6	1	NM_014797.3	ENSP00000230122.4

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59294 AN: 151410 Hom.: 11706 Cov.: 30

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.392 AC: 59353 AN: 151528 Hom.: 11718 Cov.: 30 AF XY: 0.397 AC XY: 29420 AN XY: 74046

African (AFR) AF: 0.430 AC: 17742 AN: 41266

American (AMR) AF: 0.401 AC: 6099 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1521 AN: 3466

East Asian (EAS) AF: 0.480 AC: 2469 AN: 5142

South Asian (SAS) AF: 0.421 AC: 2023 AN: 4806

European-Finnish (FIN) AF: 0.443 AC: 4636 AN: 10470

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23661 AN: 67862

Other (OTH) AF: 0.387 AC: 812 AN: 2096

Alfa AF: 0.365 Hom.: 1252

Bravo AF: 0.388

Asia WGS AF: 0.455 AC: 1581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.21
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6911838; hg19: chr6-109799923;