rs4281830

chr19-56421916-G-Achr19-56421916-G-Cchr19-56421916-G-T

Variant summary

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

The NM_152478.3(ZNF583):c.233-975G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,992 control chromosomes in the GnomAD database, including 22,547 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 0.54 (22547 hom., cov: 32)
• Consequence: ZNF583 NM_152478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

ZNF583 (HGNC:26427): (zinc finger protein 583) 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF583	NM_152478.3	c.233-975G>A		intron_variant		ENST00000333201.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF583	ENST00000333201.13	c.233-975G>A		intron_variant		2	NM_152478.3	P1
ZNF583	ENST00000291598.11	c.233-975G>A		intron_variant		3		P1
ZNF583	ENST00000391778.3	c.233-975G>A		intron_variant		4
ZNF583	ENST00000537943.5	c.233-975G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81815 AN: 151874 Hom.: 22520 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.539 AC: 81889 AN: 151992 Hom.: 22547 Cov.: 32 AF XY: 0.545 AC XY: 40464 AN XY: 74302

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.518

Alfa AF: 0.524 Hom.: 5607

Bravo AF: 0.534

Asia WGS AF: 0.729 AC: 2530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.1
Dann	Benign	0.31

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: rs4281830; hg19: chr19-56933285;