rs2262909

chr19-21952468-A-C

Variant summary

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

The ENST00000599916.5(ZNF208):c.306-19231T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,680 control chromosomes in the GnomAD database, including 46,675 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 0.78 (46675 hom., cov: 33)
• Consequence: ZNF208 ENST00000599916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

Genes affected

ZNF208 (HGNC:12999): (zinc finger protein 208) Zinc finger proteins (ZNFs), such as ZNF208, bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. A conserved protein motif, termed the Kruppel-associated box (KRAB) domain, mediates protein-protein interactions (Eichler et al., 1998 [PubMed 9724325]). See ZNF91 (MIM 603971) for further information on ZNFs.[supplied by OMIM, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF208	NM_001329971.2	c.306-11044T>G		intron_variant
ZNF208	NM_001329974.2	c.227-11044T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF208	ENST00000599916.5	c.306-19231T>G		intron_variant		1
ZNF208	ENST00000601773.5	c.227-11044T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.778 AC: 117939 AN: 151560 Hom.: 46621 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.622

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.778 AC: 118053 AN: 151680 Hom.: 46675 Cov.: 33 AF XY: 0.776 AC XY: 57559 AN XY: 74142

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.727

Alfa AF: 0.757 Hom.: 5350

Bravo AF: 0.783

Asia WGS AF: 0.650 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.3
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: rs2262909; hg19: chr19-22135270;