rs808373

chr19-22286431-G-Cchr19-22286431-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 19-22286431-G-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,466,980 control chromosomes in the GnomAD database, including 165,144 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 0.47 (16209 hom., cov: 22)
  • Exomes 𝑓: 0.47 (148935 hom.)
• Consequence: ZNF729 NM_001242680.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

Genes affected

ZNF729 (HGNC:32464): (zinc finger protein 729) Predicted to enable DNA-binding transcription activator 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF729	NM_001242680.2			upstream_gene_variant		ENST00000601693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF729	ENST00000601693.2			upstream_gene_variant		2	NM_001242680.2	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 68161 AN: 146288 Hom.: 16204 Cov.: 22

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.469 AC: 619158 AN: 1320576 Hom.: 148935 Cov.: 19 AF XY: 0.462 AC XY: 303642 AN XY: 657900

Gnomad4 AFR exome AF: 0.476

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.466 AC: 68189 AN: 146404 Hom.: 16209 Cov.: 22 AF XY: 0.459 AC XY: 32615 AN XY: 71032

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.449

Alfa AF: 0.480 Hom.: 2203

Bravo AF: 0.473

Asia WGS AF: 0.259 AC: 901 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.66
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs808373; hg19: chr19-22469233; COSMIC: COSV62603505;