rs17508595

Variant names:

• chr2-184618381-C-G
• rs17508595
• NM_194250.2:c.111+19311C>G

Variant summary

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

The NM_194250.2(ZNF804A):​c.111+19311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,938 control chromosomes in the GnomAD database, including 4,759 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 0.24 (4759 hom., cov: 33)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801
• Publications: 9 publications found

Genes affected

ZNF804A (HGNC:21711): (zinc finger protein 804A) The protein encoded by this gene is a zinc finger binding protein. Polymorphisms in this gene, especially rs1344706, are thought to confer increased susceptibility to schizophrenia, bipolar disorder, and heroin addiciton. [provided by RefSeq, Nov 2015]

ZNF804A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194250.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.111+19311C>G		intron	N/A	NP_919226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.111+19311C>G		intron	N/A	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37192 AN: 151822 Hom.: 4759 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.245 AC: 37212 AN: 151938 Hom.: 4759 Cov.: 33 AF XY: 0.247 AC XY: 18356 AN XY: 74258

African (AFR) AF: 0.231 AC: 9572 AN: 41426

American (AMR) AF: 0.177 AC: 2694 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3470

East Asian (EAS) AF: 0.143 AC: 741 AN: 5174

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4820

European-Finnish (FIN) AF: 0.323 AC: 3405 AN: 10530

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17617 AN: 67942

Other (OTH) AF: 0.245 AC: 518 AN: 2112

Alfa AF: 0.262 Hom.: 691

Bravo AF: 0.229

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.55
DANN	Benign	0.37
PhyloP100		-0.80
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: rs17508595; hg19: chr2-185483108;