18-76415746-A-G

Position:

• chr18-76415746-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.1810+25499T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,984 control chromosomes in the GnomAD database, including 24,236 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 0.56 (24236 hom., cov: 32)
• Consequence: ZNF516 NM_014643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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]

ZNF516 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF516	NM_014643.4	c.1810+25499T>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.1810+25499T>C		intron_variant		1	NM_014643.4	ENSP00000394757.2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85414 AN: 151866 Hom.: 24214 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.562 AC: 85471 AN: 151984 Hom.: 24236 Cov.: 32 AF XY: 0.567 AC XY: 42140 AN XY: 74290

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.536

Alfa AF: 0.477 Hom.: 2211

Bravo AF: 0.550

Asia WGS AF: 0.621 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.063
DANN	Benign	0.62

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: rs2554830; hg19: chr18-74127702;