2-184915494-C-G

Variant names:

• chr2-184915494-C-G
• rs4666998
• NM_194250.2:c.256-18109C>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.256-18109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,838 control chromosomes in the GnomAD database, including 24,690 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 0.56 (24690 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 5 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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.256-18109C>G		intron_variant	Intron 2 of 3	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.256-18109C>G		intron_variant	Intron 2 of 3	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84674 AN: 151718 Hom.: 24681 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.558 AC: 84711 AN: 151838 Hom.: 24690 Cov.: 32 AF XY: 0.559 AC XY: 41442 AN XY: 74164

African (AFR) AF: 0.395 AC: 16370 AN: 41454

American (AMR) AF: 0.692 AC: 10532 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4347 AN: 5160

South Asian (SAS) AF: 0.546 AC: 2635 AN: 4826

European-Finnish (FIN) AF: 0.590 AC: 6221 AN: 10546

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.599 AC: 40645 AN: 67862

Other (OTH) AF: 0.577 AC: 1213 AN: 2102

Alfa AF: 0.429 Hom.: 1192

Bravo AF: 0.565

Asia WGS AF: 0.649 AC: 2254 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		2.3
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: rs4666998; hg19: chr2-185780221;