rs1465434

Positions:

• chr19-37424330-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152484.3(ZNF569):​c.238+1538C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,056 control chromosomes in the GnomAD database, including 1,223 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 0.11 (1223 hom., cov: 31)
• Consequence: ZNF569 NM_152484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

Genes affected

ZNF569 (HGNC:24737): (zinc finger protein 569) 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 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF569	NM_152484.3	c.238+1538C>T		intron_variant		ENST00000316950.11	NP_689697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF569	ENST00000316950.11	c.238+1538C>T		intron_variant		1	NM_152484.3	ENSP00000325018	P2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17040 AN: 151938 Hom.: 1224 Cov.: 31

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.112 AC: 17032 AN: 152056 Hom.: 1223 Cov.: 31 AF XY: 0.110 AC XY: 8208 AN XY: 74300

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.114

Alfa AF: 0.147 Hom.: 353

Bravo AF: 0.104

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1465434; hg19: chr19-37915232;