19-44095462-C-T

Variant names:

• chr19-44095462-C-T
• rs4459653
• NM_001321645.3:c.-157-881C>T

Variant summary

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

The NM_001321645.3(ZNF224):​c.-157-881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,078 control chromosomes in the GnomAD database, including 43,981 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 0.75 (43976 hom., cov: 31)
  • Exomes 𝑓: 0.86 (5 hom.)
• Consequence: ZNF224 NM_001321645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 11 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321645.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF224	NM_001321645.3	MANE Select	c.-157-881C>T		intron	N/A	NP_001308574.1
	ZNF224	NM_013398.5		c.-157-881C>T		intron	N/A	NP_037530.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF224	ENST00000693561.1	MANE Select	c.-157-881C>T		intron	N/A	ENSP00000508532.1
	ZNF224	ENST00000336976.10	TSL:1	c.-157-881C>T		intron	N/A	ENSP00000337368.5
	ZNF224	ENST00000589060.1	TSL:6	n.1073C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114667 AN: 151946 Hom.: 43954 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.857 AC: 12 AN: 14 Hom.: 5 Cov.: 0 AF XY: 0.857 AC XY: 12 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 6 AN: 6

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.754 AC: 114720 AN: 152064 Hom.: 43976 Cov.: 31 AF XY: 0.749 AC XY: 55671 AN XY: 74346

African (AFR) AF: 0.641 AC: 26566 AN: 41442

American (AMR) AF: 0.727 AC: 11120 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3152 AN: 5152

South Asian (SAS) AF: 0.726 AC: 3505 AN: 4826

European-Finnish (FIN) AF: 0.785 AC: 8291 AN: 10568

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56772 AN: 68010

Other (OTH) AF: 0.784 AC: 1655 AN: 2110

Alfa AF: 0.798 Hom.: 22629

Bravo AF: 0.744

Asia WGS AF: 0.686 AC: 2386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4459653; hg19: chr19-44599615;