rs2112527

Variant names:

• chr19-9493075-A-G
• rs2112527
• NM_152476.3:c.-57+5053T>C

Variant summary

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

The NM_152476.3(ZNF560):​c.-57+5053T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,222 control chromosomes in the GnomAD database, including 2,586 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 0.15 (2586 hom., cov: 31)
• Consequence: ZNF560 NM_152476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 7 publications found

Genes affected

ZNF560 (HGNC:26484): (zinc finger protein 560) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF560	NM_152476.3	c.-57+5053T>C		intron_variant	Intron 2 of 9	ENST00000301480.5	NP_689689.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF560	ENST00000301480.5	c.-57+5053T>C		intron_variant	Intron 2 of 9	1	NM_152476.3	ENSP00000301480.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22866 AN: 152104 Hom.: 2575 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.151 AC: 22915 AN: 152222 Hom.: 2586 Cov.: 31 AF XY: 0.149 AC XY: 11058 AN XY: 74438

African (AFR) AF: 0.310 AC: 12887 AN: 41506

American (AMR) AF: 0.131 AC: 2000 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3468

East Asian (EAS) AF: 0.0386 AC: 200 AN: 5180

South Asian (SAS) AF: 0.198 AC: 955 AN: 4822

European-Finnish (FIN) AF: 0.0431 AC: 458 AN: 10618

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0808 AC: 5499 AN: 68018

Other (OTH) AF: 0.159 AC: 336 AN: 2116

Alfa AF: 0.106 Hom.: 638

Bravo AF: 0.163

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.50
PhyloP100		-0.67
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: rs2112527; hg19: chr19-9603751;