dbSNP rs61739290: ZNF804A:p.Ile492Val (chr2-184936870-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.054 ( 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

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ZNF804A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2 link	c.1474A>G	p.Ile492Val	missense_variant	Exon 4 of 4	ENST00000302277.7	NP_919226.1	Q7Z570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 link	c.1474A>G	p.Ile492Val	missense_variant	Exon 4 of 4	1	NM_194250.2	ENSP00000303252.6		Q7Z570

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

GnomAD2 exomes

AF:

0.0537

AC:

13412

AN:

249618

AF XY:

0.0557

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 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

African (AFR)

AF:

0.0249

AC:

834

AN:

33438

American (AMR)

AF:

0.0326

AC:

1452

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

2035

AN:

26056

East Asian (EAS)

AF:

0.0225

AC:

892

AN:

39670

South Asian (SAS)

AF:

0.0421

AC:

3628

AN:

86168

European-Finnish (FIN)

AF:

0.0399

AC:

2132

AN:

53394

Middle Eastern (MID)

AF:

0.0816

AC:

470

AN:

5760

European-Non Finnish (NFE)

AF:

0.0747

AC:

83014

AN:

1111436

Other (OTH)

AF:

0.0643

AC:

3877

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

4609

9219

13828

18438

23047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3016

6032

9048

12064

15080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0536

AC:

8154

AN:

152266

Hom.:

266

Cov.:

AF XY:

0.0516

AC XY:

3839

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0268

AC:

1116

AN:

41566

American (AMR)

AF:

0.0512

AC:

782

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0801

AC:

278

AN:

3472

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5182

South Asian (SAS)

AF:

0.0468

AC:

226

AN:

4830

European-Finnish (FIN)

AF:

0.0365

AC:

388

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0744

AC:

5059

AN:

68006

Other (OTH)

AF:

0.0548

AC:

116

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

402

804

1205

1607

2009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0684

Hom.:

1256

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

Dec 09, 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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.094

(source)

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;.

PhyloP100

-0.061

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over