rs7873730

chr9-111541399-A-T

Variant summary

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

The NM_133464.5(ZNF483):c.722-258A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 148,474 control chromosomes in the GnomAD database, including 1,139 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 0.11 (1139 hom., cov: 32)
• Consequence: ZNF483 NM_133464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.917

Genes affected

ZNF483 (HGNC:23384): (zinc finger protein 483) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF483	NM_133464.5	c.722-258A>T		intron_variant		ENST00000309235.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF483	ENST00000309235.6	c.722-258A>T		intron_variant		1	NM_133464.5	P1
ZNF483	ENST00000358151.8	c.721+7046A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 16716 AN: 148356 Hom.: 1141 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0698

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0529

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.113 AC: 16732 AN: 148474 Hom.: 1139 Cov.: 32 AF XY: 0.113 AC XY: 8206 AN XY: 72660

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0529

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0994 Hom.: 91

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.5
Dann	Benign	0.37

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: rs7873730; hg19: chr9-114303679;