18-14079223-C-G

Variant names:

• chr18-14079223-C-G
• rs6505873
• ENST00000589203.5:n.609-925G>C

Variant summary

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

The ENST00000589203.5(ZNF519):​n.609-925G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,020 control chromosomes in the GnomAD database, including 4,989 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 (4989 hom., cov: 32)
• Consequence: ZNF519 ENST00000589203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF519	NR_033354.2	n.591-925G>C		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF519	ENST00000589203.5	n.609-925G>C		intron_variant	Intron 4 of 5	1
ZNF519	ENST00000587419.5	n.*178-925G>C		intron_variant	Intron 3 of 4	2		ENSP00000468250.1
ZNF519	ENST00000592049.5	n.439-925G>C		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36958 AN: 151902 Hom.: 4983 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.243 AC: 36985 AN: 152020 Hom.: 4989 Cov.: 32 AF XY: 0.241 AC XY: 17943 AN XY: 74318

African (AFR) AF: 0.328 AC: 13600 AN: 41434

American (AMR) AF: 0.182 AC: 2778 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.104 AC: 499 AN: 4816

European-Finnish (FIN) AF: 0.318 AC: 3356 AN: 10560

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15195 AN: 67982

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.225 Hom.: 532

Bravo AF: 0.235

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs6505873; hg19: chr18-14079222;