rs2232447

Variant names:

• chr6-109466556-G-C
• rs2232447
• NM_014797.3:c.1389C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-109466556-G-C
• chr6-109466556-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014797.3(ZBTB24):​c.1389C>G​(p.Ser463Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,612,386 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (80 hom.)
• Consequence: ZBTB24 NM_014797.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0160
• Publications: 1 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: DEFINITIVE, STRONG Submitted by: ClinGen, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-109466556-G-C is Benign according to our data. Variant chr6-109466556-G-C is described in ClinVar as Benign. ClinVar VariationId is 472198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014797.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	NM_014797.3	MANE Select	c.1389C>G	p.Ser463Ser	synonymous	Exon 7 of 7	NP_055612.2	O43167-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.1389C>G	p.Ser463Ser	synonymous	Exon 7 of 7	ENSP00000230122.4	O43167-1
	ZBTB24	ENST00000698519.1		c.1139C>G	p.Pro380Arg	missense	Exon 5 of 5	ENSP00000513768.1	A0A8V8TNL7
	ZBTB24	ENST00000698516.1		c.1389C>G	p.Ser463Ser	synonymous	Exon 7 of 7	ENSP00000513766.1	O43167-1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2736 AN: 152134 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00434 AC: 1080 AN: 248688 AF XY: 0.00330

Gnomad AFR exome AF: 0.0625

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00180 AC: 2621 AN: 1460134 Hom.: 80 Cov.: 33 AF XY: 0.00150 AC XY: 1088 AN XY: 726470

African (AFR) AF: 0.0648 AC: 2170 AN: 33476

American (AMR) AF: 0.00275 AC: 123 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51688

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.0000647 AC: 72 AN: 1111998

Other (OTH) AF: 0.00396 AC: 239 AN: 60388

GnomAD4 genome AF: 0.0180 AC: 2742 AN: 152252 Hom.: 93 Cov.: 32 AF XY: 0.0174 AC XY: 1299 AN XY: 74458

African (AFR) AF: 0.0631 AC: 2620 AN: 41532

American (AMR) AF: 0.00529 AC: 81 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68008

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00583 Hom.: 5

Bravo AF: 0.0201

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		0.016
Mutation Taster		=93/7	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: rs2232447; hg19: chr6-109787759;