19-30452770-A-G

Variant summary

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

The NM_014717.3(ZNF536):c.2170+7038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,798 control chromosomes in the GnomAD database, including 27,013 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 0.59 (27013 hom., cov: 30)
• Consequence: ZNF536 NM_014717.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_014717.3	c.2170+7038A>G		intron_variant		ENST00000355537.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000355537.4	c.2170+7038A>G		intron_variant		1	NM_014717.3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89779 AN: 151680 Hom.: 26965 Cov.: 30

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.592 AC: 89891 AN: 151798 Hom.: 27013 Cov.: 30 AF XY: 0.586 AC XY: 43458 AN XY: 74178

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.559

Alfa AF: 0.605 Hom.: 55329

Bravo AF: 0.585

Asia WGS AF: 0.364 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	14
Dann	Benign	0.63

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: rs33436; hg19: chr19-30943677;