ENST00000592946.1:n.325-1718G>A

Variant names:

• chr19-44110055-C-T
• rs2061333
• ENST00000592946.1:n.325-1718G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000592946.1(ZNF225-AS1):​n.325-1718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,134 control chromosomes in the GnomAD database, including 40,474 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 0.72 (40474 hom., cov: 33)
• Consequence: ZNF225-AS1 ENST00000592946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 22 publications found

Genes affected

ZNF225-AS1 (HGNC:55916): (ZNF225 and ZNF224 antisense RNA 1)

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000592946.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF225-AS1	NR_033341.1		n.363-1718G>A		intron	N/A
	ZNF224	NM_001321645.3	MANE Select	c.*1771C>T		downstream_gene	N/A	NP_001308574.1
	ZNF224	NM_013398.5		c.*1771C>T		downstream_gene	N/A	NP_037530.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF225-AS1	ENST00000592946.1	TSL:1	n.325-1718G>A		intron	N/A
	ZNF225-AS1	ENST00000661725.1		n.363-1718G>A		intron	N/A
	ZNF224	ENST00000693561.1	MANE Select	c.*1771C>T		downstream_gene	N/A	ENSP00000508532.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109228 AN: 152016 Hom.: 40453 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.718 AC: 109282 AN: 152134 Hom.: 40474 Cov.: 33 AF XY: 0.709 AC XY: 52718 AN XY: 74366

African (AFR) AF: 0.588 AC: 24420 AN: 41498

American (AMR) AF: 0.584 AC: 8923 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2749 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2846 AN: 5158

South Asian (SAS) AF: 0.684 AC: 3298 AN: 4824

European-Finnish (FIN) AF: 0.773 AC: 8180 AN: 10586

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56406 AN: 68004

Other (OTH) AF: 0.750 AC: 1584 AN: 2112

Alfa AF: 0.783 Hom.: 145134

Bravo AF: 0.699

Asia WGS AF: 0.600 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.6
DANN	Benign	0.78
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs2061333; hg19: chr19-44614208;