Genetic Variant ENSG00000283839:n.475A>T (chr2-184598458-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000640078.1(ENSG00000283839):n.475A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,232 control chromosomes in the GnomAD database, including 24,556 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 0.56 ( 24515 hom., cov: 33)

Exomes 𝑓: 0.48 ( 41 hom. )

Consequence

ENSG00000283839
ENST00000640078.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.91

Publications

14 publications found

Variant links:

Genes affected

ENSG00000283839 (HGNC:):

ENSG00000283839 links:

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105373780	NR_171621.1 link	n.465A>T		non_coding_transcript_exon_variant	Exon 2 of 3
ZNF804A	NM_194250.2 link	c.-502T>A		upstream_gene_variant		ENST00000302277.7	NP_919226.1	Q7Z570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 link	c.-502T>A		upstream_gene_variant		1	NM_194250.2	ENSP00000303252.6		Q7Z570

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84319

AN:

150802

Hom.:

24512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.481

AC:

155

AN:

322

Hom.:

Cov.:

AF XY:

0.486

AC XY:

108

AN XY:

222

show subpopulations

African (AFR)

AF:

0.583

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0909

AC:

AN:

South Asian (SAS)

AF:

0.875

AC:

AN:

European-Finnish (FIN)

AF:

0.611

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.496

AC:

119

AN:

240

Other (OTH)

AF:

0.438

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.559

AC:

84346

AN:

150910

Hom.:

24515

Cov.:

AF XY:

0.551

AC XY:

40613

AN XY:

73726

show subpopulations

African (AFR)

AF:

0.662

AC:

27395

AN:

41388

American (AMR)

AF:

0.413

AC:

6269

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

1761

AN:

3462

East Asian (EAS)

AF:

0.161

AC:

820

AN:

5102

South Asian (SAS)

AF:

0.474

AC:

2287

AN:

4828

European-Finnish (FIN)

AF:

0.529

AC:

5339

AN:

10100

Middle Eastern (MID)

AF:

0.630

AC:

184

AN:

292

European-Non Finnish (NFE)

AF:

0.572

AC:

38638

AN:

67570

Other (OTH)

AF:

0.550

AC:

1150

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1894

3788

5683

7577

9471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.570

Hom.:

3151

Bravo

AF:

0.553

Asia WGS

AF:

0.323

AC:

1057

AN:

3274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

2.9

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=286/14

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