rs826323

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-37014051-G-A
• chr19-37014051-G-T

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF420	XM_011526503.3	c.-125+5969G>A		intron_variant	Intron 1 of 4		XP_011524805.1
ZNF420	XM_047438230.1	c.-158+5969G>A		intron_variant	Intron 1 of 5		XP_047294186.1
ZNF420	XM_011526510.3	c.-122+5969G>A		intron_variant	Intron 1 of 2		XP_011524812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF420	ENST00000587029.5	c.-125+5969G>A		intron_variant	Intron 1 of 4	4		ENSP00000466057.1
ZNF420	ENST00000590332.1	c.-78+5969G>A		intron_variant	Intron 1 of 1	4		ENSP00000468387.1
ENSG00000300522	ENST00000772564.1	n.221+3710G>A		intron_variant	Intron 1 of 1

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 v4.3

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;