rs258575

Positions:

• chr19-20001455-T-C

Variant summary

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

The ENST00000596019.5(ZNF682):​c.227-4192A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,186 control chromosomes in the GnomAD database, including 2,547 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 0.17 (2547 hom., cov: 32)
• Consequence: ZNF682 ENST00000596019.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

Genes affected

ZNF682 (HGNC:28857): (zinc finger protein 682) 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, DNA-templated. 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF682	XR_007067033.1	n.3345+3181A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF682	ENST00000596019.5	c.227-4192A>G		intron_variant		5		ENSP00000472444

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26486 AN: 152068 Hom.: 2541 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.174 AC: 26506 AN: 152186 Hom.: 2547 Cov.: 32 AF XY: 0.173 AC XY: 12903 AN XY: 74402

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.171

Alfa AF: 0.175 Hom.: 306

Bravo AF: 0.174

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs258575; hg19: chr19-20112264;