19-44100937-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001321645.3(ZNF224):c.142+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,440 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (25 hom., cov: 31)
  • Exomes 𝑓: 0.00089 (24 hom.)
• Consequence: ZNF224 NM_001321645.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.420

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-44100937-G-A is Benign according to our data. Variant chr19-44100937-G-A is described in ClinVar as [Benign]. Clinvar id is 777498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0082 (1248/152212) while in subpopulation AFR AF= 0.0288 (1197/41526). AF 95% confidence interval is 0.0275. There are 25 homozygotes in gnomad4. There are 556 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF224	NM_001321645.3	c.142+10G>A		intron_variant		ENST00000693561.1
ZNF224	NM_013398.5	c.142+10G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF224	ENST00000693561.1	c.142+10G>A		intron_variant			NM_001321645.3	P1

Frequencies

GnomAD3 genomes AF: 0.00817 AC: 1242 AN: 152094 Hom.: 24 Cov.: 31

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00214 AC: 535 AN: 250576 Hom.: 8 AF XY: 0.00148 AC XY: 200 AN XY: 135432

Gnomad AFR exome AF: 0.0294

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000887 AC: 1296 AN: 1461228 Hom.: 24 Cov.: 65 AF XY: 0.000802 AC XY: 583 AN XY: 726926

Gnomad4 AFR exome AF: 0.0324

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00820 AC: 1248 AN: 152212 Hom.: 25 Cov.: 31 AF XY: 0.00747 AC XY: 556 AN XY: 74424

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00644 Hom.: 3

Bravo AF: 0.00906

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.46
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs112763415; hg19: chr19-44605090; COSMIC: COSV61242126; COSMIC: COSV61242126;