18-14062350-A-C

Variant names:

• chr18-14062350-A-C
• rs2159942
• ENST00000592345.5:n.714-4835T>G

Variant summary

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

The ENST00000592345.5(ZNF519):​n.714-4835T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,180 control chromosomes in the GnomAD database, including 3,813 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 0.22 (3813 hom., cov: 31)
• Consequence: ZNF519 ENST00000592345.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 1 publications found

Genes affected

ZNF519 (HGNC:30574): (zinc finger protein 519) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Predicted to be involved in regulation of transcription, DNA-templated. 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 = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000592345.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF519	ENST00000592345.5	TSL:3	n.714-4835T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32828 AN: 152062 Hom.: 3816 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.216 AC: 32823 AN: 152180 Hom.: 3813 Cov.: 31 AF XY: 0.214 AC XY: 15933 AN XY: 74412

African (AFR) AF: 0.194 AC: 8047 AN: 41522

American (AMR) AF: 0.181 AC: 2768 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.106 AC: 514 AN: 4828

European-Finnish (FIN) AF: 0.321 AC: 3394 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16539 AN: 67986

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.208 Hom.: 1899

Bravo AF: 0.204

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.30

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2159942;

hg19: chr18-14062349;