18-76471019-T-C

Position:

• chr18-76471019-T-C

Variant summary

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

The NM_014643.4(ZNF516):​c.-271-7878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,298 control chromosomes in the GnomAD database, including 386 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 0.070 (386 hom., cov: 32)
• Consequence: ZNF516 NM_014643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF516	NM_014643.4	c.-271-7878A>G		intron_variant		ENST00000443185.7	NP_055458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF516	ENST00000443185.7	c.-271-7878A>G		intron_variant		1	NM_014643.4	ENSP00000394757	P1
ZNF516	ENST00000532857.1	c.-158+19662A>G		intron_variant		2		ENSP00000446211

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10695 AN: 152180 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0703 AC: 10702 AN: 152298 Hom.: 386 Cov.: 32 AF XY: 0.0695 AC XY: 5179 AN XY: 74480

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0632 Hom.: 162

Bravo AF: 0.0717

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.1
DANN	Benign	0.83

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: rs6565887; hg19: chr18-74182975;