rs7873730

Variant names:

• chr9-111541399-A-T
• rs7873730
• NM_133464.5:c.722-258A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133464.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF483	NM_133464.5	MANE Select	c.722-258A>T		intron	N/A	NP_597721.2	Q8TF39-1
	ZNF483	NM_001007169.6		c.721+7046A>T		intron	N/A	NP_001007170.1	Q8TF39-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF483	ENST00000309235.6	TSL:1 MANE Select	c.722-258A>T		intron	N/A	ENSP00000311679.5	Q8TF39-1
	ZNF483	ENST00000904413.1		c.722-258A>T		intron	N/A	ENSP00000574477.1
	ZNF483	ENST00000904421.1		c.722-258A>T		intron	N/A	ENSP00000574481.1

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

African (AFR) AF: 0.160 AC: 6520 AN: 40624

American (AMR) AF: 0.145 AC: 2121 AN: 14654

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 166 AN: 3140

East Asian (EAS) AF: 0.261 AC: 1345 AN: 5162

South Asian (SAS) AF: 0.119 AC: 566 AN: 4768

European-Finnish (FIN) AF: 0.0741 AC: 784 AN: 10584

Middle Eastern (MID) AF: 0.106 AC: 28 AN: 264

European-Non Finnish (NFE) AF: 0.0743 AC: 4934 AN: 66420

Other (OTH) AF: 0.104 AC: 208 AN: 1998

Alfa AF: 0.0994 Hom.: 91

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.37
PhyloP100		0.92
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: rs7873730; hg19: chr9-114303679; COSMIC: COSV107361108; COSMIC: COSV107361108;