rs7258628

Positions:

• chr19-30678014-T-C

Variant summary

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

The NM_001376110.1(ZNF536):​c.3896-32743T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,188 control chromosomes in the GnomAD database, including 616 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 0.067 (616 hom., cov: 33)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_001352260.2	c.*27-32743T>C		intron_variant
ZNF536	NM_001376110.1	c.3896-32743T>C		intron_variant
ZNF536	NM_001376111.1	c.3896-32743T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000592773.3	c.3896-32743T>C		intron_variant		5		P1
ZNF536	ENST00000706143.1	c.1649-32743T>C		intron_variant
ZNF536	ENST00000706147.1	c.2324-32743T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10210 AN: 152070 Hom.: 608 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0680

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

GnomAD4 genome AF: 0.0673 AC: 10246 AN: 152188 Hom.: 616 Cov.: 33 AF XY: 0.0647 AC XY: 4818 AN XY: 74424

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.0673

Alfa AF: 0.0447 Hom.: 257

Bravo AF: 0.0746

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7258628; hg19: chr19-31168921;