rs524802

Positions:

• chr19-36956045-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.359-18375G>A		intron_variant			NP_001191767.1
ZNF568	NM_001204839.2	c.167-18375G>A		intron_variant			NP_001191768.1
ZNF568	XM_017026772.2	c.359-18375G>A		intron_variant			XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000427117.6	c.359-18375G>A		intron_variant		1		ENSP00000407012
ZNF568	ENST00000444991.6	c.359-18375G>A		intron_variant		1		ENSP00000389794
ZNF568	ENST00000455427.7	c.167-18375G>A		intron_variant		2		ENSP00000413396

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

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.351

Alfa AF: 0.353 Hom.: 1170

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs524802; hg19: chr19-37446947;