NM_015461.3:c.3658+36123C>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

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 = 0.569 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

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.433

Alfa AF: 0.448 Hom.: 2886

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

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: rs7229946; hg19: chr18-22739001;