rs3217319

chr19-52300416-CTG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144684.4(ZNF480):c.9_10del(p.Cys3Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,612,698 control chromosomes in the GnomAD database, including 415,545 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31645 hom., cov: 0)
  • Exomes 𝑓: 0.72 (383900 hom.)
• Consequence: ZNF480 NM_144684.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

Genes affected

ZNF480 (HGNC:23305): (zinc finger protein 480) 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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-52300416-CTG-C is Benign according to our data. Variant chr19-52300416-CTG-C is described in ClinVar as [Benign]. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF480	NM_144684.4	c.9_10del	p.Cys3Ter	frameshift_variant	2/5	ENST00000595962.6
ZNF480	NM_001297624.2	c.9_10del	p.Cys3Ter	frameshift_variant	2/4
ZNF480	NM_001297625.2	c.-96_-95del		5_prime_UTR_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF480	ENST00000595962.6	c.9_10del	p.Cys3Ter	frameshift_variant	2/5	1	NM_144684.4	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95257 AN: 151508 Hom.: 31650 Cov.: 0

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.642

GnomAD3 exomes AF: 0.691 AC: 173530 AN: 251220 Hom.: 61168 AF XY: 0.701 AC XY: 95241 AN XY: 135790

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.631

Gnomad SAS exome AF: 0.728

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.702

GnomAD4 exome AF: 0.722 AC: 1054817 AN: 1461072 Hom.: 383900 AF XY: 0.722 AC XY: 525143 AN XY: 726888

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.635

Gnomad4 EAS exome AF: 0.664

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.695

GnomAD4 genome AF: 0.628 AC: 95265 AN: 151626 Hom.: 31645 Cov.: 0 AF XY: 0.634 AC XY: 46961 AN XY: 74060

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.640

Alfa AF: 0.675 Hom.: 6504

Bravo AF: 0.609

Asia WGS AF: 0.631 AC: 2193 AN: 3478

EpiCase AF: 0.722

EpiControl AF: 0.729

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 7679/12518=61.35% -

Computational scores

Source: dbNSFP v4.3

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: rs3217319; hg19: chr19-52803669;