2-184903127-C-T

Variant names:

• chr2-184903127-C-T
• rs1366840
• NM_194250.2:c.256-30476C>T

Variant summary

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

The NM_194250.2(ZNF804A):​c.256-30476C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,876 control chromosomes in the GnomAD database, including 17,536 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 0.44 (17536 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.256-30476C>T		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.256-30476C>T		intron_variant	Intron 2 of 3	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67414 AN: 151756 Hom.: 17540 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.444 AC: 67420 AN: 151876 Hom.: 17536 Cov.: 32 AF XY: 0.449 AC XY: 33326 AN XY: 74222

African (AFR) AF: 0.165 AC: 6822 AN: 41462

American (AMR) AF: 0.616 AC: 9382 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3468

East Asian (EAS) AF: 0.819 AC: 4202 AN: 5132

South Asian (SAS) AF: 0.497 AC: 2389 AN: 4810

European-Finnish (FIN) AF: 0.553 AC: 5830 AN: 10536

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35444 AN: 67914

Other (OTH) AF: 0.467 AC: 984 AN: 2108

Alfa AF: 0.507 Hom.: 35279

Bravo AF: 0.443

Asia WGS AF: 0.594 AC: 2067 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.77
DANN	Benign	0.34
PhyloP100		-0.70
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: rs1366840; hg19: chr2-185767854;