Variant rs4667001 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.47 ( 20580 hom., cov: 31)

Exomes 𝑓: 0.58 ( 253423 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.56

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804A	NM_194250.2 linkuse as main transcript	c.1624G>A	p.Glu542Lys	missense_variant	4/4	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 linkuse as main transcript	c.1624G>A	p.Glu542Lys	missense_variant	4/4	1	NM_194250.2	ENSP00000303252	P1

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71764

AN:

151584

Hom.:

20583

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.594

AC:

147519

AN:

248450

Hom.:

46630

AF XY:

0.591

AC XY:

79730

AN XY:

134800

show subpopulations

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 SAS exome

AF:

0.543

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.:

AF XY:

0.581

AC XY:

422100

AN XY:

726474

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.708

Gnomad4 ASJ exome

AF:

0.610

Gnomad4 EAS exome

AF:

0.844

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.582

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.473

AC:

71762

AN:

151702

Hom.:

20580

Cov.:

AF XY:

0.479

AC XY:

35497

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.606

Gnomad4 EAS

AF:

0.831

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.626

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.551

Hom.:

26832

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

LINK: link

Submissions by phenotype

ZNF804A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0000010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.038

Sift

Benign

0.11

T;.

Sift4G

Benign

0.22

T;T

Polyphen

0.012

B;.

Vest4

0.025

MPC

0.039

ClinPred

0.0025

GERP RS

3.2

Varity_R

0.093

gMVP

0.11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over