rs33428

Variant names:

• chr19-30446936-A-G
• rs33428
• NM_014717.3:c.2170+1204A>G

Variant summary

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

The NM_014717.3(ZNF536):​c.2170+1204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,126 control chromosomes in the GnomAD database, including 38,611 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 0.70 (38611 hom., cov: 33)
• Consequence: ZNF536 NM_014717.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 5 publications found

Genes affected

ZNF536 (HGNC:29025): (zinc finger protein 536) The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation. [provided by RefSeq, Sep 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF536	NM_014717.3	c.2170+1204A>G		intron_variant	Intron 2 of 4	ENST00000355537.4	NP_055532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF536	ENST00000355537.4	c.2170+1204A>G		intron_variant	Intron 2 of 4	1	NM_014717.3	ENSP00000347730.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107113 AN: 152008 Hom.: 38562 Cov.: 33

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.705 AC: 107228 AN: 152126 Hom.: 38611 Cov.: 33 AF XY: 0.694 AC XY: 51605 AN XY: 74368

African (AFR) AF: 0.800 AC: 33207 AN: 41516

American (AMR) AF: 0.648 AC: 9899 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2458 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1860 AN: 5162

South Asian (SAS) AF: 0.437 AC: 2099 AN: 4808

European-Finnish (FIN) AF: 0.695 AC: 7351 AN: 10580

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47784 AN: 68002

Other (OTH) AF: 0.702 AC: 1482 AN: 2112

Alfa AF: 0.695 Hom.: 54679

Bravo AF: 0.705

Asia WGS AF: 0.436 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.43
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs33428; hg19: chr19-30937843;