rs12985487

chr19-52562408-A-G

Variant summary

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

The ENST00000487863.5(ZNF808):c.*423-910A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 152,178 control chromosomes in the GnomAD database, including 271 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 0.058 (271 hom., cov: 32)
• Consequence: ZNF808 ENST00000487863.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

Genes affected

ZNF808 (HGNC:33230): (zinc finger protein 808) Predicted to enable DNA-binding transcription activator 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]

ZNF701 (HGNC:25597): (zinc finger protein 701) 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF808	XR_002958314.2	n.3300-910A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF808	ENST00000487863.5	c.*423-910A>G		intron_variant, NMD_transcript_variant		1
ZNF701	ENST00000478039.1	n.229+6358A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8793 AN: 152062 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0578 AC: 8794 AN: 152178 Hom.: 271 Cov.: 32 AF XY: 0.0581 AC XY: 4320 AN XY: 74400

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.0579

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0910

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0642 Hom.: 450

Bravo AF: 0.0553

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.3
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12985487; hg19: chr19-53065661;