19-30452770-A-G

Variant names:

• chr19-30452770-A-G
• rs33436
• NM_014717.3:c.2170+7038A>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+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
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF536	NM_014717.3	MANE Select	c.2170+7038A>G		intron	N/A	NP_055532.1	O15090
	ZNF536	NM_001376110.1		c.2170+7038A>G		intron	N/A	NP_001363039.1	K7EQN6
	ZNF536	NM_001376111.1		c.2170+7038A>G		intron	N/A	NP_001363040.1	K7EQN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF536	ENST00000355537.4	TSL:1 MANE Select	c.2170+7038A>G		intron	N/A	ENSP00000347730.1	O15090
	ZNF536	ENST00000592773.3	TSL:5	c.2170+7038A>G		intron	N/A	ENSP00000467909.3	K7EQN6
	ZNF536	ENST00000706148.1		c.2170+7038A>G		intron	N/A	ENSP00000516231.1	A0A994J7Z0

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

African (AFR) AF: 0.570 AC: 23570 AN: 41370

American (AMR) AF: 0.583 AC: 8899 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1762 AN: 5138

South Asian (SAS) AF: 0.371 AC: 1777 AN: 4796

European-Finnish (FIN) AF: 0.655 AC: 6912 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 42953 AN: 67908

Other (OTH) AF: 0.559 AC: 1179 AN: 2108

Alfa AF: 0.607 Hom.: 118791

Bravo AF: 0.585

Asia WGS AF: 0.364 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs33436; hg19: chr19-30943677;