rs10441737

chr9-111539305-C-T

Variant summary

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

The NM_133464.5(ZNF483):c.722-2352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 348,348 control chromosomes in the GnomAD database, including 61,437 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 0.59 (26502 hom., cov: 31)
  • Exomes 𝑓: 0.59 (34935 hom.)
• Consequence: ZNF483 NM_133464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF483	NM_133464.5	c.722-2352C>T		intron_variant		ENST00000309235.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF483	ENST00000309235.6	c.722-2352C>T		intron_variant		1	NM_133464.5	P1
ZNF483	ENST00000355824.7	c.722-141C>T		intron_variant		1
ZNF483	ENST00000358151.8	c.721+4952C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88851 AN: 151858 Hom.: 26488 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.588 AC: 115478 AN: 196372 Hom.: 34935 AF XY: 0.582 AC XY: 64285 AN XY: 110430

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.585 AC: 88909 AN: 151976 Hom.: 26502 Cov.: 31 AF XY: 0.577 AC XY: 42889 AN XY: 74300

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.564

Alfa AF: 0.628 Hom.: 49661

Bravo AF: 0.572

Asia WGS AF: 0.480 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	8.2
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: rs10441737; hg19: chr9-114301585; COSMIC: COSV58515047;