rs11702690

Positions:

• chr21-41987559-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098402.2(ZBTB21):​c.*3336T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 152,324 control chromosomes in the GnomAD database, including 268 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 0.051 (268 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBTB21 NM_001098402.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920

Genes affected

ZBTB21 (HGNC:13083): (zinc finger and BTB domain containing 21) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; POZ domain binding activity; and methyl-CpG binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB21	NM_001098402.2	c.*3336T>C		3_prime_UTR_variant	3/3	ENST00000310826.10	NP_001091872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB21	ENST00000310826	c.*3336T>C		3_prime_UTR_variant	3/3	1	NM_001098402.2	ENSP00000308759.5
ZBTB21	ENST00000398505	c.*3336T>C		3_prime_UTR_variant	4/4	1		ENSP00000381517.3

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7765 AN: 152206 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00616

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0568

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0509 AC: 7756 AN: 152324 Hom.: 268 Cov.: 32 AF XY: 0.0501 AC XY: 3728 AN XY: 74484

Gnomad4 AFR AF: 0.0139

Gnomad4 AMR AF: 0.0370

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00617

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0771

Gnomad4 OTH AF: 0.0562

Alfa AF: 0.0689 Hom.: 296

Bravo AF: 0.0463

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.0
DANN	Benign	0.65

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: rs11702690; hg19: chr21-43407668;