NM_001001415.4:c.4-8915A>G

Variant names:

• chr19-21520743-A-G
• rs2650757
• NM_001001415.4:c.4-8915A>G

Variant summary

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

The NM_001001415.4(ZNF429):​c.4-8915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,182 control chromosomes in the GnomAD database, including 3,015 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 0.20 (3015 hom., cov: 32)
• Consequence: ZNF429 NM_001001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 12 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]

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 = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF429	NM_001001415.4	c.4-8915A>G		intron_variant	Intron 1 of 3	ENST00000358491.9	NP_001001415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF429	ENST00000358491.9	c.4-8915A>G		intron_variant	Intron 1 of 3	3	NM_001001415.4	ENSP00000351280.3
ZNF429	ENST00000597078.5	c.4-8915A>G		intron_variant	Intron 1 of 5	1		ENSP00000470300.1
ZNF429	ENST00000594022.1	n.193-8341A>G		intron_variant	Intron 2 of 5	3
ZNF429	ENST00000596126.1	n.469-8341A>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29809 AN: 152064 Hom.: 3006 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.196 AC: 29846 AN: 152182 Hom.: 3015 Cov.: 32 AF XY: 0.196 AC XY: 14593 AN XY: 74396

African (AFR) AF: 0.221 AC: 9181 AN: 41506

American (AMR) AF: 0.179 AC: 2732 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3472

East Asian (EAS) AF: 0.0770 AC: 399 AN: 5182

South Asian (SAS) AF: 0.181 AC: 872 AN: 4824

European-Finnish (FIN) AF: 0.192 AC: 2030 AN: 10586

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

European-Non Finnish (NFE) AF: 0.193 AC: 13143 AN: 68014

Other (OTH) AF: 0.193 AC: 408 AN: 2112

Alfa AF: 0.196 Hom.: 570

Bravo AF: 0.198

Asia WGS AF: 0.132 AC: 455 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.35
PhyloP100		-2.3
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: rs2650757; hg19: chr19-21703545;