rs728534

Variant names:

• chr2-184937190-A-G
• rs728534
• NM_194250.2:c.1794A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-184937190-A-G
• chr2-184937190-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_194250.2(ZNF804A):​c.1794A>G​(p.Lys598Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,595,064 control chromosomes in the GnomAD database, including 33,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (2259 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30930 hom.)
• Consequence: ZNF804A NM_194250.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.00
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-184937190-A-G is Benign according to our data. Variant chr2-184937190-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060253.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.1794A>G	p.Lys598Lys	synonymous_variant	Exon 4 of 4	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.1794A>G	p.Lys598Lys	synonymous_variant	Exon 4 of 4	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23262 AN: 152064 Hom.: 2256 Cov.: 33

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.197 AC: 45328 AN: 230060 AF XY: 0.206

Gnomad AFR exome AF: 0.0343

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.201 AC: 290554 AN: 1442882 Hom.: 30930 Cov.: 47 AF XY: 0.205 AC XY: 146779 AN XY: 717646

African (AFR) AF: 0.0295 AC: 935 AN: 31736

American (AMR) AF: 0.109 AC: 4243 AN: 38826

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5137 AN: 25014

East Asian (EAS) AF: 0.236 AC: 9327 AN: 39550

South Asian (SAS) AF: 0.274 AC: 22580 AN: 82310

European-Finnish (FIN) AF: 0.231 AC: 12213 AN: 52874

Middle Eastern (MID) AF: 0.171 AC: 964 AN: 5622

European-Non Finnish (NFE) AF: 0.202 AC: 223500 AN: 1107526

Other (OTH) AF: 0.196 AC: 11655 AN: 59424

GnomAD4 genome AF: 0.153 AC: 23257 AN: 152182 Hom.: 2259 Cov.: 33 AF XY: 0.153 AC XY: 11406 AN XY: 74390

African (AFR) AF: 0.0359 AC: 1491 AN: 41556

American (AMR) AF: 0.135 AC: 2063 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1175 AN: 5178

South Asian (SAS) AF: 0.260 AC: 1252 AN: 4820

European-Finnish (FIN) AF: 0.215 AC: 2273 AN: 10576

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13652 AN: 67974

Other (OTH) AF: 0.170 AC: 359 AN: 2110

Alfa AF: 0.182 Hom.: 1398

Bravo AF: 0.142

Asia WGS AF: 0.232 AC: 805 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZNF804A-related disorder Benign:1

Nov 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.1
DANN	Benign	0.60
PhyloP100		2.0
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: rs728534; hg19: chr2-185801917; COSMIC: COSV56436034;