rs7229946

Variant names:

• chr18-25159037-G-A
• rs7229946
• NM_015461.3:c.3658+36123C>T

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+36123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,780 control chromosomes in the GnomAD database, including 14,775 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 0.44 (14775 hom., cov: 31)
• Consequence: ZNF521 NM_015461.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF521	NM_015461.3	c.3658+36123C>T		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+36123C>T		intron_variant	Intron 5 of 7	1	NM_015461.3	ENSP00000354794.3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66567 AN: 151662 Hom.: 14760 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.439 AC: 66616 AN: 151780 Hom.: 14775 Cov.: 31 AF XY: 0.441 AC XY: 32700 AN XY: 74150

African (AFR) AF: 0.439 AC: 18170 AN: 41398

American (AMR) AF: 0.378 AC: 5771 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1630 AN: 3462

East Asian (EAS) AF: 0.357 AC: 1838 AN: 5148

South Asian (SAS) AF: 0.588 AC: 2825 AN: 4808

European-Finnish (FIN) AF: 0.448 AC: 4695 AN: 10484

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.446 AC: 30291 AN: 67908

Other (OTH) AF: 0.433 AC: 912 AN: 2108

Alfa AF: 0.435 Hom.: 6394

Bravo AF: 0.426

Asia WGS AF: 0.465 AC: 1618 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	1.5
DANN	Benign	0.46
PhyloP100		0.22
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: rs7229946; hg19: chr18-22739001;