chr11-114063972-C-G

Variant names:

• chr11-114063972-C-G
• rs35784831
• NM_006006.6:c.672C>G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006006.6(ZBTB16):​c.672C>G​(p.Pro224Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,613,540 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P224P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (18 hom.)
• Consequence: ZBTB16 NM_006006.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.77

Genes affected

ZBTB16 (HGNC:12930): (zinc finger and BTB domain containing 16) This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-114063972-C-G is Benign according to our data. Variant chr11-114063972-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 731188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.77 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB16	NM_006006.6	c.672C>G	p.Pro224Pro	synonymous_variant	Exon 2 of 7	ENST00000335953.9	NP_005997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB16	ENST00000335953.9	c.672C>G	p.Pro224Pro	synonymous_variant	Exon 2 of 7	1	NM_006006.6	ENSP00000338157.4

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 427 AN: 152116 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00311 AC: 774 AN: 248712 Hom.: 5 AF XY: 0.00312 AC XY: 421 AN XY: 134998

Gnomad AFR exome AF: 0.000512

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.0129

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00379 AC: 5532 AN: 1461306 Hom.: 18 Cov.: 31 AF XY: 0.00369 AC XY: 2684 AN XY: 726922

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.0135

Gnomad4 NFE exome AF: 0.00383

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.00280 AC: 427 AN: 152234 Hom.: 2 Cov.: 32 AF XY: 0.00304 AC XY: 226 AN XY: 74428

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00338

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00278 Hom.: 1

Bravo AF: 0.00202

EpiCase AF: 0.00316

EpiControl AF: 0.00249

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZBTB16: BP4, BP7, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.015
DANN	Benign	0.55

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: rs35784831; hg19: chr11-113934694;