rs10016022

Positions:

• chr4-10445282-A-G
• chr4-10445282-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_053042.3(ZNF518B):​c.1047T>C​(p.Asp349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,614,078 control chromosomes in the GnomAD database, including 447,782 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 0.77 (45688 hom., cov: 33)
  • Exomes 𝑓: 0.74 (402094 hom.)
• Consequence: ZNF518B NM_053042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

Genes affected

ZNF518B (HGNC:29365): (zinc finger protein 518B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-3.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF518B	NM_053042.3	c.1047T>C	p.Asp349=	synonymous_variant	3/3	ENST00000326756.4	NP_444270.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF518B	ENST00000326756.4	c.1047T>C	p.Asp349=	synonymous_variant	3/3	3	NM_053042.3	ENSP00000317614	P1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117368 AN: 152090 Hom.: 45633 Cov.: 33

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.782

GnomAD3 exomes AF: 0.744 AC: 186970 AN: 251338 Hom.: 70005 AF XY: 0.745 AC XY: 101238 AN XY: 135840

Gnomad AFR exome AF: 0.872

Gnomad AMR exome AF: 0.674

Gnomad ASJ exome AF: 0.746

Gnomad EAS exome AF: 0.811

Gnomad SAS exome AF: 0.779

Gnomad FIN exome AF: 0.676

Gnomad NFE exome AF: 0.739

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.741 AC: 1082818 AN: 1461870 Hom.: 402094 Cov.: 73 AF XY: 0.742 AC XY: 539379 AN XY: 727228

Gnomad4 AFR exome AF: 0.880

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.795

Gnomad4 SAS exome AF: 0.774

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 0.752

GnomAD4 genome AF: 0.772 AC: 117486 AN: 152208 Hom.: 45688 Cov.: 33 AF XY: 0.768 AC XY: 57176 AN XY: 74400

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.785

Alfa AF: 0.745 Hom.: 85084

Bravo AF: 0.778

Asia WGS AF: 0.806 AC: 2806 AN: 3478

EpiCase AF: 0.738

EpiControl AF: 0.745

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.42

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: rs10016022; hg19: chr4-10446906;