18-76481807-A-G

Position:

• chr18-76481807-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014643.4(ZNF516):​c.-272+13337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,158 control chromosomes in the GnomAD database, including 42,730 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 (42730 hom., cov: 33)
• Consequence: ZNF516 NM_014643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31

Genes affected

ZNF516 (HGNC:28990): (zinc finger protein 516) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a zinc-finger protein, and belongs to the krueppel C2H2-type zinc-finger protein family. It may be involved in transcriptional regulation. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF516	NM_014643.4	c.-272+13337T>C		intron_variant		ENST00000443185.7	NP_055458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF516	ENST00000443185.7	c.-272+13337T>C		intron_variant		1	NM_014643.4	ENSP00000394757.2
ZNF516	ENST00000532857.1	c.-158+8874T>C		intron_variant		2		ENSP00000446211.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113282 AN: 152040 Hom.: 42722 Cov.: 33

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.745 AC: 113326 AN: 152158 Hom.: 42730 Cov.: 33 AF XY: 0.743 AC XY: 55242 AN XY: 74380

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.757

Alfa AF: 0.783 Hom.: 61513

Bravo AF: 0.744

Asia WGS AF: 0.652 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.10
DANN	Benign	0.34

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: rs3866685; hg19: chr18-74193763;