19-21521162-G-A

Variant names:

• chr19-21521162-G-A
• rs2681365
• NM_001001415.4:c.4-8496G>A

Variant summary

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

The NM_001001415.4(ZNF429):​c.4-8496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,100 control chromosomes in the GnomAD database, including 2,679 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 0.19 (2679 hom., cov: 32)
• Consequence: ZNF429 NM_001001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 6 publications found

Genes affected

ZNF429 (HGNC:20817): (zinc finger protein 429) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

BNIP3P26 (HGNC:49706): (BCL2 interacting protein 3 pseudogene 26)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001415.4. 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
	ZNF429	NM_001001415.4	MANE Select	c.4-8496G>A		intron	N/A	NP_001001415.2
	ZNF429	NM_001346912.2		c.17-8515G>A		intron	N/A	NP_001333841.1
	ZNF429	NM_001346913.2		c.-93-8496G>A		intron	N/A	NP_001333842.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF429	ENST00000358491.9	TSL:3 MANE Select	c.4-8496G>A		intron	N/A	ENSP00000351280.3
	ZNF429	ENST00000597078.5	TSL:1	c.4-8496G>A		intron	N/A	ENSP00000470300.1
	ZNF429	ENST00000594022.1	TSL:3	n.193-7922G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28314 AN: 151982 Hom.: 2678 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0769

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.186 AC: 28322 AN: 152100 Hom.: 2679 Cov.: 32 AF XY: 0.186 AC XY: 13858 AN XY: 74368

African (AFR) AF: 0.187 AC: 7747 AN: 41486

American (AMR) AF: 0.175 AC: 2679 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3468

East Asian (EAS) AF: 0.0771 AC: 399 AN: 5176

South Asian (SAS) AF: 0.181 AC: 872 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2033 AN: 10566

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13140 AN: 67986

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.191 Hom.: 406

Bravo AF: 0.187

Asia WGS AF: 0.127 AC: 441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.15
PhyloP100		0.091
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: rs2681365; hg19: chr19-21703964;