rs524802

Variant names:

• chr19-36956045-G-A
• rs524802
• ENST00000444991.6:c.359-18375G>A

Variant summary

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

The ENST00000444991.6(ZNF568):​c.359-18375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,976 control chromosomes in the GnomAD database, including 10,086 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 0.36 (10086 hom., cov: 31)
• Consequence: ZNF568 ENST00000444991.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 6 publications found

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) 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 embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291239 (HGNC:):

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 = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.359-18375G>A		intron_variant	Intron 6 of 9		NP_001191767.1
ZNF568	NM_001204839.2	c.167-18375G>A		intron_variant	Intron 5 of 8		NP_001191768.1
ZNF568	XM_017026772.2	c.359-18375G>A		intron_variant	Intron 6 of 9		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.359-18375G>A		intron_variant	Intron 8 of 11			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54545 AN: 151858 Hom.: 10073 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0910

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.359 AC: 54607 AN: 151976 Hom.: 10086 Cov.: 31 AF XY: 0.357 AC XY: 26525 AN XY: 74262

African (AFR) AF: 0.414 AC: 17162 AN: 41432

American (AMR) AF: 0.351 AC: 5362 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 963 AN: 3472

East Asian (EAS) AF: 0.0912 AC: 471 AN: 5162

South Asian (SAS) AF: 0.304 AC: 1467 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3617 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24642 AN: 67954

Other (OTH) AF: 0.351 AC: 743 AN: 2114

Alfa AF: 0.354 Hom.: 1225

Bravo AF: 0.363

Asia WGS AF: 0.237 AC: 824 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	8.9
DANN	Benign	0.71
PhyloP100		0.12
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: rs524802; hg19: chr19-37446947;