rs7252479

Positions:

• chr19-52505839-C-A
• chr19-52505839-C-T

Variant summary

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

The NM_001099694.2(ZNF578):​c.190+1058C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 151,984 control chromosomes in the GnomAD database, including 454 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 0.071 (454 hom., cov: 32)
• Consequence: ZNF578 NM_001099694.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

Genes affected

ZNF578 (HGNC:26449): (zinc finger protein 578) 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 located in cytoplasm. 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF578	NM_001099694.2	c.190+1058C>A		intron_variant		ENST00000421239.7	NP_001093164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF578	ENST00000421239.7	c.190+1058C>A		intron_variant		2	NM_001099694.2	ENSP00000459216	P1
ZNF578	ENST00000601120.1	c.190+1058C>A		intron_variant		5		ENSP00000470790

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10733 AN: 151880 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0185

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0771

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

GnomAD4 genome AF: 0.0707 AC: 10749 AN: 151984 Hom.: 454 Cov.: 32 AF XY: 0.0703 AC XY: 5224 AN XY: 74322

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0763

Alfa AF: 0.0493 Hom.: 93

Bravo AF: 0.0713

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.22

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: rs7252479; hg19: chr19-53009092;