18-76415746-A-G

Variant names:

• chr18-76415746-A-G
• rs2554830
• NM_014643.4:c.1810+25499T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014643.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF516	NM_014643.4	MANE Select	c.1810+25499T>C		intron	N/A	NP_055458.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF516	ENST00000443185.7	TSL:1 MANE Select	c.1810+25499T>C		intron	N/A	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

African (AFR) AF: 0.491 AC: 20351 AN: 41428

American (AMR) AF: 0.589 AC: 8993 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2773 AN: 5154

South Asian (SAS) AF: 0.681 AC: 3277 AN: 4812

European-Finnish (FIN) AF: 0.643 AC: 6808 AN: 10582

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.580 AC: 39383 AN: 67948

Other (OTH) AF: 0.536 AC: 1133 AN: 2114

Alfa AF: 0.477 Hom.: 2298

Bravo AF: 0.550

Asia WGS AF: 0.621 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.063
DANN	Benign	0.62
PhyloP100		-1.7
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: rs2554830; hg19: chr18-74127702;