19-30608983-A-G

Variant names:

• chr19-30608983-A-G
• rs746961
• NM_001376110.1:c.3895+59469A>G

Variant summary

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

The NM_001376110.1(ZNF536):​c.3895+59469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,012 control chromosomes in the GnomAD database, including 16,604 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 0.46 (16604 hom., cov: 32)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376110.1. 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_001376110.1		c.3895+59469A>G		intron	N/A	NP_001363039.1	K7EQN6
	ZNF536	NM_001376111.1		c.3895+59469A>G		intron	N/A	NP_001363040.1	K7EQN6
	ZNF536	NM_001438953.1		c.3895+59469A>G		intron	N/A	NP_001425882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF536	ENST00000592773.3	TSL:5	c.3895+59469A>G		intron	N/A	ENSP00000467909.3	K7EQN6
	ZNF536	ENST00000706148.1		c.3896-34554A>G		intron	N/A	ENSP00000516231.1	A0A994J7Z0
	ZNF536	ENST00000706150.1		c.3896-34554A>G		intron	N/A	ENSP00000516233.1	A0A994J7Z0

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70302 AN: 151894 Hom.: 16599 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.463 AC: 70334 AN: 152012 Hom.: 16604 Cov.: 32 AF XY: 0.469 AC XY: 34807 AN XY: 74294

African (AFR) AF: 0.432 AC: 17910 AN: 41446

American (AMR) AF: 0.489 AC: 7472 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3468

East Asian (EAS) AF: 0.702 AC: 3617 AN: 5152

South Asian (SAS) AF: 0.488 AC: 2352 AN: 4816

European-Finnish (FIN) AF: 0.572 AC: 6032 AN: 10554

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30033 AN: 67978

Other (OTH) AF: 0.446 AC: 943 AN: 2114

Alfa AF: 0.445 Hom.: 70855

Bravo AF: 0.454

Asia WGS AF: 0.581 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.45
PhyloP100		0.71

Splicing

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

Other links and lift over

dbSNP: rs746961; hg19: chr19-31099890;