Genetic Variant ZNF804A:c.386+44A>C (chr2-184933777-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_194250.2(ZNF804A):c.386+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,570,832 control chromosomes in the GnomAD database, including 266,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 20642 hom., cov: 31)

Exomes 𝑓: 0.58 ( 245845 hom. )

Consequence

ZNF804A
NM_194250.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.287

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2 link	c.386+44A>C		intron_variant	Intron 3 of 3	ENST00000302277.7	NP_919226.1	Q7Z570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 link	c.386+44A>C		intron_variant	Intron 3 of 3	1	NM_194250.2	ENSP00000303252.6		Q7Z570

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

71902

AN:

151706

Hom.:

20645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.503

GnomAD2 exomes

AF:

0.593

AC:

128847

AN:

217170

AF XY:

0.593

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.722

Gnomad ASJ exome

AF:

0.619

Gnomad EAS exome

AF:

0.841

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.586

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.581

AC:

824750

AN:

1419008

Hom.:

245845

Cov.:

AF XY:

0.581

AC XY:

409807

AN XY:

705684

show subpopulations

African (AFR)

AF:

0.111

AC:

3434

AN:

31048

American (AMR)

AF:

0.709

AC:

24879

AN:

35112

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15123

AN:

24790

East Asian (EAS)

AF:

0.829

AC:

32005

AN:

38592

South Asian (SAS)

AF:

0.547

AC:

43389

AN:

79282

European-Finnish (FIN)

AF:

0.642

AC:

33474

AN:

52172

Middle Eastern (MID)

AF:

0.417

AC:

2337

AN:

5602

European-Non Finnish (NFE)

AF:

0.583

AC:

637354

AN:

1093964

Other (OTH)

AF:

0.560

AC:

32755

AN:

58446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

14048

28096

42145

56193

70241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17622

35244

52866

70488

88110

<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:

0.474

AC:

71901

AN:

151824

Hom.:

20642

Cov.:

AF XY:

0.480

AC XY:

35591

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.134

AC:

5533

AN:

41444

American (AMR)

AF:

0.645

AC:

9819

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2105

AN:

3464

East Asian (EAS)

AF:

0.820

AC:

4222

AN:

5150

South Asian (SAS)

AF:

0.543

AC:

2615

AN:

4814

European-Finnish (FIN)

AF:

0.628

AC:

6614

AN:

10526

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.580

AC:

39387

AN:

67884

Other (OTH)

AF:

0.499

AC:

1050

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1579

3157

4736

6314

7893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.465

Hom.:

2695

Bravo

AF:

0.466

Asia WGS

AF:

0.615

AC:

2139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.78

(source)

DANN

Benign

0.50

PhyloP100

-0.29

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over