19-37014051-G-A

Variant names:

• chr19-37014051-G-A
• rs826323
• ENST00000587029.5:c.-125+5969G>A

Variant summary

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

The ENST00000587029.5(ZNF420):​c.-125+5969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,110 control chromosomes in the GnomAD database, including 10,522 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 (10522 hom., cov: 32)
• Consequence: ZNF420 ENST00000587029.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 7 publications found

Genes affected

ZNF420 (HGNC:20649): (zinc finger protein 420) The protein encoded by this gene is a KRAB-type zinc finger protein that negatively-regulates p53-mediated apoptosis. Under stress conditions, the encoded protein is phosphorylated by ATM and dissociates from p53, which activates p53 and initiates apoptosis. [provided by RefSeq, Jul 2016]

ENSG00000300522 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000587029.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF420	ENST00000587029.5	TSL:4	c.-125+5969G>A		intron	N/A	ENSP00000466057.1
	ZNF420	ENST00000590332.1	TSL:4	c.-78+5969G>A		intron	N/A	ENSP00000468387.1
	ENSG00000300522	ENST00000772564.1		n.221+3710G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55370 AN: 151992 Hom.: 10503 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.365 AC: 55446 AN: 152110 Hom.: 10522 Cov.: 32 AF XY: 0.361 AC XY: 26886 AN XY: 74378

African (AFR) AF: 0.454 AC: 18834 AN: 41476

American (AMR) AF: 0.352 AC: 5393 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3462

East Asian (EAS) AF: 0.0954 AC: 494 AN: 5176

South Asian (SAS) AF: 0.272 AC: 1307 AN: 4806

European-Finnish (FIN) AF: 0.341 AC: 3613 AN: 10588

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23968 AN: 67978

Other (OTH) AF: 0.348 AC: 734 AN: 2112

Alfa AF: 0.223 Hom.: 476

Bravo AF: 0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.73
DANN	Benign	0.52
PhyloP100		-2.9

Splicing

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

Other links and lift over

dbSNP: rs826323; hg19: chr19-37504953;