rs4667001

Variant names:

• chr2-184937020-G-A
• rs4667001
• NM_194250.2:c.1624G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-184937020-G-A
• chr2-184937020-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_194250.2(ZNF804A):​c.1624G>A​(p.Glu542Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,612,128 control chromosomes in the GnomAD database, including 274,003 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.47 (20580 hom., cov: 31)
  • Exomes 𝑓: 0.58 (253423 hom.)
• Consequence: ZNF804A NM_194250.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.56
• Publications: 36 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0094146E-6).
• BP6: Variant 2-184937020-G-A is Benign according to our data. Variant chr2-184937020-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059275.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.1624G>A	p.Glu542Lys	missense	Exon 4 of 4	NP_919226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.1624G>A	p.Glu542Lys	missense	Exon 4 of 4	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71764 AN: 151584 Hom.: 20583 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.501

GnomAD2 exomes AF: 0.594 AC: 147519 AN: 248450 AF XY: 0.591

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.717

Gnomad ASJ exome AF: 0.616

Gnomad EAS exome AF: 0.846

Gnomad FIN exome AF: 0.645

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.594

GnomAD4 exome AF: 0.582 AC: 849304 AN: 1460426 Hom.: 253423 Cov.: 48 AF XY: 0.581 AC XY: 422100 AN XY: 726474

African (AFR) AF: 0.113 AC: 3771 AN: 33436

American (AMR) AF: 0.708 AC: 31492 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 15901 AN: 26062

East Asian (EAS) AF: 0.844 AC: 33426 AN: 39602

South Asian (SAS) AF: 0.548 AC: 47173 AN: 86144

European-Finnish (FIN) AF: 0.641 AC: 34182 AN: 53366

Middle Eastern (MID) AF: 0.416 AC: 2392 AN: 5754

European-Non Finnish (NFE) AF: 0.582 AC: 647194 AN: 1111276

Other (OTH) AF: 0.560 AC: 33773 AN: 60310

GnomAD4 genome AF: 0.473 AC: 71762 AN: 151702 Hom.: 20580 Cov.: 31 AF XY: 0.479 AC XY: 35497 AN XY: 74104

African (AFR) AF: 0.133 AC: 5516 AN: 41428

American (AMR) AF: 0.643 AC: 9803 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2097 AN: 3462

East Asian (EAS) AF: 0.831 AC: 4277 AN: 5146

South Asian (SAS) AF: 0.543 AC: 2612 AN: 4814

European-Finnish (FIN) AF: 0.626 AC: 6568 AN: 10484

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39293 AN: 67822

Other (OTH) AF: 0.497 AC: 1046 AN: 2106

Alfa AF: 0.533 Hom.: 42929

Bravo AF: 0.465

TwinsUK AF: 0.586 AC: 2172

ALSPAC AF: 0.603 AC: 2323

ESP6500AA AF: 0.140 AC: 603

ESP6500EA AF: 0.577 AC: 4940

ExAC AF: 0.576 AC: 69820

Asia WGS AF: 0.615 AC: 2136 AN: 3474

EpiCase AF: 0.577

EpiControl AF: 0.584

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZNF804A-related disorder Benign:1

Oct 17, 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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.038
Sift	Benign	0.11	T
Sift4G	Benign	0.22	T
Polyphen		0.012	B
Vest4		0.025
MPC		0.039
ClinPred		0.0025	T
GERP RS		3.2
Varity_R		0.093
gMVP		0.11
Mutation Taster		=97/3	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: rs4667001; hg19: chr2-185801747; COSMIC: COSV104534934;