rs17701834

Positions:

• chr19-21938656-T-G

Variant summary

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

The ENST00000599916.5(ZNF208):​c.306-5419A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,040 control chromosomes in the GnomAD database, including 1,382 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 0.12 (1382 hom., cov: 32)
• Consequence: ZNF208 ENST00000599916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF208	ENST00000599916.5	c.306-5419A>C		intron_variant		1		ENSP00000469254

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18519 AN: 151922 Hom.: 1379 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.122 AC: 18526 AN: 152040 Hom.: 1382 Cov.: 32 AF XY: 0.127 AC XY: 9460 AN XY: 74290

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0997

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.121

Alfa AF: 0.140 Hom.: 2218

Bravo AF: 0.107

Asia WGS AF: 0.136 AC: 469 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17701834; hg19: chr19-22121458;