19-30240104-C-T

Variant names:

• chr19-30240104-C-T
• rs2018622
• NM_001376110.1:c.-73+14434C>T

Variant summary

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

The NM_001376110.1(ZNF536):​c.-73+14434C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,990 control chromosomes in the GnomAD database, including 10,302 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 0.36 (10302 hom., cov: 32)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF536	NM_001376110.1	c.-73+14434C>T		intron_variant	Intron 1 of 5		NP_001363039.1
ZNF536	NM_001376111.1	c.-73+11431C>T		intron_variant	Intron 1 of 5		NP_001363040.1
ZNF536	NM_001438953.1	c.-73+12087C>T		intron_variant	Intron 1 of 5		NP_001425882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF536	ENST00000592773.3	c.-73+12087C>T		intron_variant	Intron 1 of 5	5		ENSP00000467909.3
ZNF536	ENST00000706148.1	c.-73+12087C>T		intron_variant	Intron 1 of 6			ENSP00000516231.1
ZNF536	ENST00000706142.1	c.-190+15189C>T		intron_variant	Intron 1 of 6			ENSP00000516226.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54457 AN: 151872 Hom.: 10297 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.359 AC: 54491 AN: 151990 Hom.: 10302 Cov.: 32 AF XY: 0.358 AC XY: 26629 AN XY: 74290

African (AFR) AF: 0.402 AC: 16658 AN: 41432

American (AMR) AF: 0.434 AC: 6642 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3462

East Asian (EAS) AF: 0.615 AC: 3177 AN: 5162

South Asian (SAS) AF: 0.512 AC: 2461 AN: 4808

European-Finnish (FIN) AF: 0.194 AC: 2047 AN: 10564

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20800 AN: 67954

Other (OTH) AF: 0.404 AC: 851 AN: 2108

Alfa AF: 0.192 Hom.: 1025

Bravo AF: 0.375

Asia WGS AF: 0.534 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.82
PhyloP100		-0.074

Splicing

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

Other links and lift over

dbSNP: rs2018622; hg19: chr19-30731011;