2-184817003-C-G

Variant names:

• chr2-184817003-C-G
• rs17584522
• NM_194250.2:c.112-49366C>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.112-49366C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,696 control chromosomes in the GnomAD database, including 2,854 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 0.18 (2854 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801
• Publications: 7 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

ENSG00000299447 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.287 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.112-49366C>G		intron	N/A	NP_919226.1	Q7Z570

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.112-49366C>G		intron	N/A	ENSP00000303252.6	Q7Z570
	ENSG00000299447	ENST00000763602.1		n.163-8101G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26705 AN: 151578 Hom.: 2859 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.176 AC: 26699 AN: 151696 Hom.: 2854 Cov.: 32 AF XY: 0.177 AC XY: 13084 AN XY: 74116

African (AFR) AF: 0.0626 AC: 2590 AN: 41400

American (AMR) AF: 0.226 AC: 3428 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3460

East Asian (EAS) AF: 0.299 AC: 1539 AN: 5142

South Asian (SAS) AF: 0.157 AC: 756 AN: 4820

European-Finnish (FIN) AF: 0.223 AC: 2344 AN: 10518

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14926 AN: 67866

Other (OTH) AF: 0.164 AC: 346 AN: 2104

Alfa AF: 0.0949 Hom.: 148

Bravo AF: 0.173

Asia WGS AF: 0.208 AC: 728 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	1.4
DANN	Benign	0.38
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: rs17584522; hg19: chr2-185681730;