rs10131416

Variant names:

• chr14-64477555-C-G
• rs10131416
• ENST00000555220.5:c.173+12806G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304508.1(ZBTB25):​c.173+12806G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,978 control chromosomes in the GnomAD database, including 5,726 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 0.27 (5726 hom., cov: 32)
• Consequence: ZBTB25 NM_001304508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB25	NM_001304508.1		c.173+12806G>C		intron	N/A	NP_001291437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB25	ENST00000555220.5	TSL:1	c.173+12806G>C		intron	N/A	ENSP00000450718.1
	ZBTB25	ENST00000555424.1	TSL:5	c.256+9559G>C		intron	N/A	ENSP00000451046.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40687 AN: 151860 Hom.: 5728 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.268 AC: 40695 AN: 151978 Hom.: 5726 Cov.: 32 AF XY: 0.269 AC XY: 19999 AN XY: 74264

African (AFR) AF: 0.187 AC: 7744 AN: 41450

American (AMR) AF: 0.216 AC: 3304 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2137 AN: 5160

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4814

European-Finnish (FIN) AF: 0.310 AC: 3264 AN: 10536

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21134 AN: 67960

Other (OTH) AF: 0.269 AC: 568 AN: 2110

Alfa AF: 0.287 Hom.: 860

Bravo AF: 0.257

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10131416; hg19: chr14-64944273;