Variant rs61739290 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.1474A>G(p.Ile492Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,613,082 control chromosomes in the GnomAD database, including 3,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.054 ( 266 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3573 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0610

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=0.0024322867).

BP6

Variant 2-184936870-A-G is Benign according to our data. Variant chr2-184936870-A-G is described in ClinVar as [Benign]. Clinvar id is 3055535.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0727 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.1474A>G	p.Ile492Val	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.1474A>G	p.Ile492Val	missense_variant	4/4	1	NM_194250.2	ENSP00000303252	P1

Frequencies

GnomAD3 genomes

AF:

0.0536

AC:

8160

AN:

152148

Hom.:

266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0269

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.0513

Gnomad ASJ

AF:

0.0801

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0744

Gnomad OTH

AF:

0.0559

GnomAD3 exomes

AF:

0.0537

AC:

13412

AN:

249618

Hom.:

455

AF XY:

0.0557

AC XY:

7532

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.0793

Gnomad EAS exome

AF:

0.0166

Gnomad SAS exome

AF:

0.0408

Gnomad FIN exome

AF:

0.0364

Gnomad NFE exome

AF:

0.0747

Gnomad OTH exome

AF:

0.0603

GnomAD4 exome

AF:

0.0673

AC:

98334

AN:

1460816

Hom.:

3573

Cov.:

AF XY:

0.0669

AC XY:

48616

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.0249

Gnomad4 AMR exome

AF:

0.0326

Gnomad4 ASJ exome

AF:

0.0781

Gnomad4 EAS exome

AF:

0.0225

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.0399

Gnomad4 NFE exome

AF:

0.0747

Gnomad4 OTH exome

AF:

0.0643

GnomAD4 genome

AF:

0.0536

AC:

8154

AN:

152266

Hom.:

266

Cov.:

AF XY:

0.0516

AC XY:

3839

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0268

Gnomad4 AMR

AF:

0.0512

Gnomad4 ASJ

AF:

0.0801

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.0468

Gnomad4 FIN

AF:

0.0365

Gnomad4 NFE

AF:

0.0744

Gnomad4 OTH

AF:

0.0548

Alfa

AF:

0.0705

Hom.:

651

Bravo

AF:

0.0537

TwinsUK

AF:

0.0779

AC:

289

ALSPAC

AF:

0.0708

AC:

273

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.0778

AC:

669

ExAC

AF:

0.0543

AC:

6595

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.0792

EpiControl

AF:

0.0797

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

Dec 09, 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

0.064

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.094

DANN

Benign

0.14

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.11

N;.

REVEL

Benign

0.040

Sift

Benign

0.24

T;.

Sift4G

Benign

0.50

T;T

Polyphen

0.0010

B;.

Vest4

0.015

MPC

0.20

ClinPred

0.0076

GERP RS

-5.0

Varity_R

0.025

gMVP

0.052

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