rs4508518

Variant names:

• chr19-44107267-A-G
• rs4508518
• NM_001321645.3:c.1107A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-44107267-A-G
• chr19-44107267-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001321645.3(ZNF224):​c.1107A>G​(p.Glu369Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,582,610 control chromosomes in the GnomAD database, including 505,767 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 0.74 (42217 hom., cov: 32)
  • Exomes 𝑓: 0.80 (463550 hom.)
• Consequence: ZNF224 NM_001321645.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 25 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]

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.499 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF224	NM_001321645.3	c.1107A>G	p.Glu369Glu	synonymous_variant	Exon 6 of 6	ENST00000693561.1	NP_001308574.1
ZNF224	NM_013398.5	c.1107A>G	p.Glu369Glu	synonymous_variant	Exon 6 of 6		NP_037530.2
ZNF225-AS1	NR_033341.1	n.1433T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF224	ENST00000693561.1	c.1107A>G	p.Glu369Glu	synonymous_variant	Exon 6 of 6		NM_001321645.3	ENSP00000508532.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112122 AN: 151950 Hom.: 42190 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.759

GnomAD2 exomes AF: 0.721 AC: 161962 AN: 224612 AF XY: 0.731

Gnomad AFR exome AF: 0.660

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.795

Gnomad EAS exome AF: 0.544

Gnomad FIN exome AF: 0.746

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.757

GnomAD4 exome AF: 0.800 AC: 1144390 AN: 1430542 Hom.: 463550 Cov.: 82 AF XY: 0.799 AC XY: 566429 AN XY: 709310

African (AFR) AF: 0.655 AC: 21223 AN: 32406

American (AMR) AF: 0.506 AC: 20174 AN: 39854

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 18827 AN: 23736

East Asian (EAS) AF: 0.540 AC: 21363 AN: 39538

South Asian (SAS) AF: 0.688 AC: 55449 AN: 80638

European-Finnish (FIN) AF: 0.744 AC: 38670 AN: 51988

Middle Eastern (MID) AF: 0.767 AC: 4299 AN: 5602

European-Non Finnish (NFE) AF: 0.837 AC: 918536 AN: 1097804

Other (OTH) AF: 0.777 AC: 45849 AN: 58976

GnomAD4 genome AF: 0.738 AC: 112189 AN: 152068 Hom.: 42217 Cov.: 32 AF XY: 0.727 AC XY: 53997 AN XY: 74322

African (AFR) AF: 0.666 AC: 27611 AN: 41458

American (AMR) AF: 0.590 AC: 9021 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2778 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2822 AN: 5152

South Asian (SAS) AF: 0.682 AC: 3294 AN: 4830

European-Finnish (FIN) AF: 0.740 AC: 7818 AN: 10566

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56364 AN: 67992

Other (OTH) AF: 0.756 AC: 1597 AN: 2112

Alfa AF: 0.795 Hom.: 99128

Bravo AF: 0.723

Asia WGS AF: 0.600 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.2
DANN	Benign	0.50
PhyloP100		-0.50
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: rs4508518; hg19: chr19-44611420; COSMIC: COSV61242212; COSMIC: COSV61242212;