rs475188

chr19-52646714-C-Achr19-52646714-C-Gchr19-52646714-C-T

Variant summary

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

The NM_001277948.2(ZNF83):c.-448-11561G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,966 control chromosomes in the GnomAD database, including 20,445 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 0.51 (20445 hom., cov: 31)
• Consequence: ZNF83 NM_001277948.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

Genes affected

ZNF83 (HGNC:13158): (zinc finger protein 83) 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 located 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF83	NM_001277948.2	c.-448-11561G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF83	ENST00000687234.1	c.142+8847G>T		intron_variant
ZNF83	ENST00000706197.1	c.-73-11561G>T		intron_variant
ZNF83	ENST00000594682.6	c.142+8847G>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77325 AN: 151848 Hom.: 20395 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.510 AC: 77428 AN: 151966 Hom.: 20445 Cov.: 31 AF XY: 0.510 AC XY: 37862 AN XY: 74272

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.487

Alfa AF: 0.428 Hom.: 7802

Bravo AF: 0.526

Asia WGS AF: 0.550 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.13
Dann	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs475188; hg19: chr19-53149967;