rs1465434

Variant names:

• chr19-37424330-G-A
• rs1465434
• NM_152484.3:c.238+1538C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF569	NM_152484.3	c.238+1538C>T		intron_variant	Intron 5 of 5	ENST00000316950.11	NP_689697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF569	ENST00000316950.11	c.238+1538C>T		intron_variant	Intron 5 of 5	1	NM_152484.3	ENSP00000325018.5

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

African (AFR) AF: 0.0300 AC: 1247 AN: 41514

American (AMR) AF: 0.106 AC: 1616 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.0810 AC: 420 AN: 5184

South Asian (SAS) AF: 0.0806 AC: 388 AN: 4816

European-Finnish (FIN) AF: 0.142 AC: 1492 AN: 10532

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10960 AN: 67956

Other (OTH) AF: 0.114 AC: 241 AN: 2106

Alfa AF: 0.144 Hom.: 355

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
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1465434; hg19: chr19-37915232;