rs4802207

Positions:

• chr19-44096224-C-T

Variant summary

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

The NM_001321645.3(ZNF224):​c.-157-119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,986 control chromosomes in the GnomAD database, including 34,635 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 0.64 (34635 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZNF224 NM_001321645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

Genes affected

ZNF224 (HGNC:13017): (zinc finger protein 224) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein represses transcription of the aldolase A gene, which encodes a key enzyme in glycolysis. The encoded zinc-finger protein may also function as a transcriptional co-activator with Wilms' tumor protein 1 to regulate apoptotic genes in leukemia. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF224	NM_001321645.3	c.-157-119C>T		intron_variant		ENST00000693561.1	NP_001308574.1
ZNF224	NM_013398.5	c.-157-119C>T		intron_variant			NP_037530.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF224	ENST00000693561.1	c.-157-119C>T		intron_variant			NM_001321645.3	ENSP00000508532	P1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97044 AN: 151868 Hom.: 34633 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.690

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.639 AC: 97048 AN: 151986 Hom.: 34635 Cov.: 32 AF XY: 0.631 AC XY: 46892 AN XY: 74304

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.688

Alfa AF: 0.798 Hom.: 96087

Bravo AF: 0.610

Asia WGS AF: 0.577 AC: 2004 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.95
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4802207; hg19: chr19-44600377;