17-12019847-A-T

Variant names:

• chr17-12019847-A-T
• rs3809728
• ENST00000578024.1:n.24+1476T>A

Variant summary

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

The ENST00000578024.1(ENSG00000293152):​n.24+1476T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,144 control chromosomes in the GnomAD database, including 4,074 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 0.23 (4074 hom., cov: 32)
• Consequence: ENSG00000293152 ENST00000578024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 10 publications found

Genes affected

ENSG00000293152 (HGNC:):

ZNF18 (HGNC:12969): (zinc finger protein 18) Predicted to enable DNA-binding transcription factor 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. Predicted to be located in nucleus. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF18	XM_024450911.2	c.-329+1476T>A		intron_variant	Intron 1 of 8		XP_024306679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293152	ENST00000578024.1	n.24+1476T>A		intron_variant	Intron 1 of 1	4
ENSG00000293152	ENST00000579522.1	n.186+1476T>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34509 AN: 152028 Hom.: 4070 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.227 AC: 34527 AN: 152144 Hom.: 4074 Cov.: 32 AF XY: 0.226 AC XY: 16782 AN XY: 74350

African (AFR) AF: 0.177 AC: 7336 AN: 41532

American (AMR) AF: 0.244 AC: 3727 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3472

East Asian (EAS) AF: 0.187 AC: 970 AN: 5176

South Asian (SAS) AF: 0.172 AC: 829 AN: 4814

European-Finnish (FIN) AF: 0.273 AC: 2881 AN: 10558

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17178 AN: 67988

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.129 Hom.: 247

Bravo AF: 0.226

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.74
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs3809728; hg19: chr17-11923164;