chr19-37040829-G-C

Variant names:

• chr19-37040829-G-C
• rs7246739
• ENST00000587029.5:c.-125+32747G>C

Variant summary

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

The ENST00000587029.5(ZNF420):​c.-125+32747G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,822 control chromosomes in the GnomAD database, including 25,523 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 0.56 (25523 hom., cov: 31)
• Consequence: ZNF420 ENST00000587029.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF420	XM_011526503.3	c.-125+32747G>C		intron_variant	Intron 1 of 4		XP_011524805.1
ZNF420	XM_047438230.1	c.-158+32747G>C		intron_variant	Intron 1 of 5		XP_047294186.1
ZNF420	XM_011526510.3	c.-122+32747G>C		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+32747G>C		intron_variant	Intron 1 of 4	4		ENSP00000466057.1
ZNF420	ENST00000590332.1	c.-78+32747G>C		intron_variant	Intron 1 of 1	4		ENSP00000468387.1
ENSG00000300522	ENST00000772564.1	n.222-20217G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85159 AN: 151704 Hom.: 25478 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.562 AC: 85276 AN: 151822 Hom.: 25523 Cov.: 31 AF XY: 0.555 AC XY: 41205 AN XY: 74208

African (AFR) AF: 0.761 AC: 31498 AN: 41384

American (AMR) AF: 0.527 AC: 8031 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1565 AN: 3464

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5162

South Asian (SAS) AF: 0.409 AC: 1963 AN: 4800

European-Finnish (FIN) AF: 0.502 AC: 5287 AN: 10536

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34326 AN: 67912

Other (OTH) AF: 0.556 AC: 1172 AN: 2108

Alfa AF: 0.533 Hom.: 2781

Bravo AF: 0.574

Asia WGS AF: 0.376 AC: 1309 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	6.6
DANN	Benign	0.32
PhyloP100		0.091

Splicing

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

Other links and lift over

dbSNP: rs7246739; hg19: chr19-37531731;