chr2-184624494-C-G

Variant names:

• chr2-184624494-C-G
• rs12613195
• NM_194250.2:c.111+25424C>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.111+25424C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,068 control chromosomes in the GnomAD database, including 6,217 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 0.26 (6217 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.111+25424C>G		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+25424C>G		intron_variant	Intron 1 of 3	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39382 AN: 151952 Hom.: 6221 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.259 AC: 39383 AN: 152068 Hom.: 6217 Cov.: 32 AF XY: 0.265 AC XY: 19659 AN XY: 74318

African (AFR) AF: 0.0841 AC: 3495 AN: 41542

American (AMR) AF: 0.315 AC: 4813 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2507 AN: 5166

South Asian (SAS) AF: 0.288 AC: 1385 AN: 4812

European-Finnish (FIN) AF: 0.384 AC: 4060 AN: 10582

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21208 AN: 67910

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.273 Hom.: 801

Bravo AF: 0.249

Asia WGS AF: 0.363 AC: 1260 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.28
PhyloP100		-0.45
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: rs12613195; hg19: chr2-185489221;