14-64463914-A-G

Position:

• chr14-64463914-A-G

Variant summary

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

The ENST00000555220.5(ZBTB25):​c.174-14276T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,110 control chromosomes in the GnomAD database, including 8,979 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 0.34 (8979 hom., cov: 32)
• Consequence: ZBTB25 ENST00000555220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB25	NM_001304508.1	c.174-14276T>C		intron_variant			NP_001291437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB25	ENST00000555220.5	c.174-14276T>C		intron_variant		1		ENSP00000450718
ZBTB25	ENST00000555424.1	c.257-14276T>C		intron_variant		5		ENSP00000451046

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51897 AN: 151992 Hom.: 8979 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.341 AC: 51923 AN: 152110 Hom.: 8979 Cov.: 32 AF XY: 0.345 AC XY: 25642 AN XY: 74324

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.339

Alfa AF: 0.339 Hom.: 18289

Bravo AF: 0.337

Asia WGS AF: 0.418 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs745686; hg19: chr14-64930632;