rs2262909

Variant names:

• chr19-21952468-A-C
• rs2262909
• ENST00000599916.5:c.306-19231T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF208	NM_001329971.2	c.306-11044T>G		intron_variant	Intron 4 of 4		NP_001316900.1
ZNF208	NM_001329974.2	c.227-11044T>G		intron_variant	Intron 3 of 3		NP_001316903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF208	ENST00000599916.5	c.306-19231T>G		intron_variant	Intron 4 of 4	1		ENSP00000469254.1
ZNF208	ENST00000601773.5	c.227-11044T>G		intron_variant	Intron 3 of 3	2		ENSP00000469887.1

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

African (AFR) AF: 0.921 AC: 38206 AN: 41472

American (AMR) AF: 0.735 AC: 11188 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2124 AN: 3462

East Asian (EAS) AF: 0.807 AC: 4110 AN: 5090

South Asian (SAS) AF: 0.549 AC: 2647 AN: 4818

European-Finnish (FIN) AF: 0.812 AC: 8586 AN: 10574

Middle Eastern (MID) AF: 0.617 AC: 179 AN: 290

European-Non Finnish (NFE) AF: 0.720 AC: 48780 AN: 67742

Other (OTH) AF: 0.727 AC: 1529 AN: 2104

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2262909; hg19: chr19-22135270;