rs722385

Variant names:

• chr2-184611323-C-T
• rs722385
• NM_194250.2:c.111+12253C>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.111+12253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 151,954 control chromosomes in the GnomAD database, including 1,167 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 (1167 hom., cov: 31)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.111+12253C>T		intron_variant	Intron 1 of 3	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.111+12253C>T		intron_variant	Intron 1 of 3	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16556 AN: 151836 Hom.: 1169 Cov.: 31

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.109 AC: 16544 AN: 151954 Hom.: 1167 Cov.: 31 AF XY: 0.105 AC XY: 7826 AN XY: 74250

African (AFR) AF: 0.0295 AC: 1222 AN: 41448

American (AMR) AF: 0.0989 AC: 1508 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3472

East Asian (EAS) AF: 0.0248 AC: 128 AN: 5162

South Asian (SAS) AF: 0.0714 AC: 345 AN: 4830

European-Finnish (FIN) AF: 0.141 AC: 1484 AN: 10514

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11098 AN: 67968

Other (OTH) AF: 0.115 AC: 243 AN: 2104

Alfa AF: 0.146 Hom.: 4660

Bravo AF: 0.103

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.45
PhyloP100		-0.37
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: rs722385; hg19: chr2-185476050;