rs10145013

Positions:

• chr14-64474873-C-T

Variant summary

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

The ENST00000555220.5(ZBTB25):​c.173+15488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,032 control chromosomes in the GnomAD database, including 5,156 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 0.24 (5156 hom., cov: 32)
• Consequence: ZBTB25 ENST00000555220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

Genes affected

ZBTB25 (HGNC:13112): (zinc finger and BTB domain containing 25) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB25	NM_001304508.1	c.173+15488G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB25	ENST00000555220.5	c.173+15488G>A		intron_variant		1
ZBTB25	ENST00000555424.1	c.256+12241G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36652 AN: 151914 Hom.: 5159 Cov.: 32

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.241 AC: 36648 AN: 152032 Hom.: 5156 Cov.: 32 AF XY: 0.244 AC XY: 18116 AN XY: 74298

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.252

Alfa AF: 0.292 Hom.: 6482

Bravo AF: 0.226

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10145013; hg19: chr14-64941591;