rs8083432

Variant names:

• chr18-25151396-A-C
• rs8083432
• NM_015461.3:c.3658+43764T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015461.3(ZNF521):​c.3658+43764T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,084 control chromosomes in the GnomAD database, including 3,668 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 0.22 (3668 hom., cov: 31)
• Consequence: ZNF521 NM_015461.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 8 publications found

Genes affected

ZNF521 (HGNC:24605): (zinc finger protein 521) Enables protein domain specific binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within neuron fate commitment. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000298287 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF521	NM_015461.3	c.3658+43764T>G		intron_variant	Intron 5 of 7	ENST00000361524.8	NP_056276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF521	ENST00000361524.8	c.3658+43764T>G		intron_variant	Intron 5 of 7	1	NM_015461.3	ENSP00000354794.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32965 AN: 151966 Hom.: 3665 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.217 AC: 32986 AN: 152084 Hom.: 3668 Cov.: 31 AF XY: 0.217 AC XY: 16116 AN XY: 74340

African (AFR) AF: 0.242 AC: 10046 AN: 41498

American (AMR) AF: 0.210 AC: 3213 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3468

East Asian (EAS) AF: 0.126 AC: 655 AN: 5184

South Asian (SAS) AF: 0.160 AC: 772 AN: 4818

European-Finnish (FIN) AF: 0.251 AC: 2647 AN: 10546

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14064 AN: 67976

Other (OTH) AF: 0.229 AC: 483 AN: 2108

Alfa AF: 0.208 Hom.: 10911

Bravo AF: 0.216

Asia WGS AF: 0.155 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.52
PhyloP100		-0.37
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: rs8083432; hg19: chr18-22731360;