rs994653

Variant names:

• chr2-184645258-G-A
• rs994653
• NM_194250.2:c.111+46188G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-184645258-G-A
• chr2-184645258-G-C

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+46188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,056 control chromosomes in the GnomAD database, including 1,414 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 0.11 (1414 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.281 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.111+46188G>A		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.111+46188G>A		intron	N/A	ENSP00000303252.6	Q7Z570

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17064 AN: 151938 Hom.: 1410 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.112 AC: 17071 AN: 152056 Hom.: 1414 Cov.: 32 AF XY: 0.115 AC XY: 8553 AN XY: 74338

African (AFR) AF: 0.0310 AC: 1287 AN: 41512

American (AMR) AF: 0.243 AC: 3707 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1520 AN: 5174

South Asian (SAS) AF: 0.154 AC: 743 AN: 4822

European-Finnish (FIN) AF: 0.0830 AC: 877 AN: 10572

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.118 AC: 7982 AN: 67926

Other (OTH) AF: 0.127 AC: 267 AN: 2106

Alfa AF: 0.116 Hom.: 153

Bravo AF: 0.123

Asia WGS AF: 0.199 AC: 686 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.079
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: rs994653; hg19: chr2-185509985;