chr19-56421916-G-A

Variant names:

• chr19-56421916-G-A
• rs4281830
• NM_152478.3:c.233-975G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152478.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF583	NM_152478.3	MANE Select	c.233-975G>A		intron	N/A	NP_689691.2
	ZNF583	NM_001159860.2		c.233-975G>A		intron	N/A	NP_001153332.1
	ZNF583	NM_001159861.2		c.233-975G>A		intron	N/A	NP_001153333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF583	ENST00000333201.13	TSL:2 MANE Select	c.233-975G>A		intron	N/A	ENSP00000388502.2
	ZNF583	ENST00000291598.11	TSL:3	c.233-975G>A		intron	N/A	ENSP00000291598.7
	ZNF583	ENST00000391778.3	TSL:4	c.233-975G>A		intron	N/A	ENSP00000375657.3

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

African (AFR) AF: 0.491 AC: 20339 AN: 41434

American (AMR) AF: 0.591 AC: 9025 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3468

East Asian (EAS) AF: 0.879 AC: 4543 AN: 5170

South Asian (SAS) AF: 0.624 AC: 3013 AN: 4828

European-Finnish (FIN) AF: 0.608 AC: 6423 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35237 AN: 67934

Other (OTH) AF: 0.518 AC: 1095 AN: 2114

Alfa AF: 0.524 Hom.: 5722

Bravo AF: 0.534

Asia WGS AF: 0.729 AC: 2530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-1.2
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: rs4281830; hg19: chr19-56933285;