rs11702690

Variant names:

• chr21-41987559-A-G
• rs11702690
• NM_001098402.2:c.*3336T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZBTB21	NM_001098402.2	c.*3336T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000310826.10	NP_001091872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB21	ENST00000310826.10	c.*3336T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001098402.2	ENSP00000308759.5
ZBTB21	ENST00000398505.7	c.*3336T>C		3_prime_UTR_variant	Exon 4 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0139 AC: 577 AN: 41572

American (AMR) AF: 0.0370 AC: 566 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.00617 AC: 32 AN: 5186

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4828

European-Finnish (FIN) AF: 0.0747 AC: 792 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5246 AN: 68030

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0682 Hom.: 335

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
PhyloP100		0.92
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: rs11702690; hg19: chr21-43407668;