2-184918414-T-C

Variant names:

• chr2-184918414-T-C
• rs1583048
• NM_194250.2:c.256-15189T>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.256-15189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,122 control chromosomes in the GnomAD database, including 2,247 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 0.15 (2247 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 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.256-15189T>C		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.256-15189T>C		intron	N/A	ENSP00000303252.6	Q7Z570

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23050 AN: 152004 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.151 AC: 23043 AN: 152122 Hom.: 2247 Cov.: 32 AF XY: 0.152 AC XY: 11320 AN XY: 74368

African (AFR) AF: 0.0405 AC: 1683 AN: 41536

American (AMR) AF: 0.218 AC: 3330 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1556 AN: 5156

South Asian (SAS) AF: 0.126 AC: 610 AN: 4830

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10580

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12824 AN: 67966

Other (OTH) AF: 0.146 AC: 308 AN: 2112

Alfa AF: 0.172 Hom.: 6731

Bravo AF: 0.151

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.57
PhyloP100		-0.10
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: rs1583048; hg19: chr2-185783141;