Genetic Variant NPAS3:c.-437C>T (chr14-33214911-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000547068.5(NPAS3):c.-437C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 440,672 control chromosomes in the GnomAD database, including 152,328 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 0.78 ( 47511 hom., cov: 32)

Exomes 𝑓: 0.85 ( 104817 hom. )

Consequence

NPAS3
ENST00000547068.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.669

Publications

4 publications found

Variant links:

Genes affected

NPAS3 (HGNC:19311): (neuronal PAS domain protein 3) This gene encodes a member of the basic helix-loop-helix and PAS domain-containing family of transcription factors. The encoded protein is localized to the nucleus and may regulate genes involved in neurogenesis. Chromosomal abnormalities that affect the coding potential of this gene are associated with schizophrenia and cognitive disability. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

NPAS3 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2 link	c.141-271C>T		intron_variant	Intron 2 of 11	ENST00000356141.9	NP_001158221.1	Q8IXF0-1X5D2Q4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9 link	c.141-271C>T		intron_variant	Intron 2 of 11	1	NM_001164749.2	ENSP00000348460.4		Q8IXF0-1

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118700

AN:

151918

Hom.:

47470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.864

Gnomad ASJ

AF:

0.899

Gnomad EAS

AF:

0.810

Gnomad SAS

AF:

0.878

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.813

GnomAD4 exome

AF:

0.850

AC:

245401

AN:

288636

Hom.:

104817

Cov.:

AF XY:

0.854

AC XY:

130380

AN XY:

152728

show subpopulations

African (AFR)

AF:

0.591

AC:

5049

AN:

8540

American (AMR)

AF:

0.902

AC:

8707

AN:

9658

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

8161

AN:

9074

East Asian (EAS)

AF:

0.822

AC:

14016

AN:

17042

South Asian (SAS)

AF:

0.877

AC:

30562

AN:

34832

European-Finnish (FIN)

AF:

0.828

AC:

12706

AN:

15348

Middle Eastern (MID)

AF:

0.881

AC:

1105

AN:

1254

European-Non Finnish (NFE)

AF:

0.857

AC:

151006

AN:

176280

Other (OTH)

AF:

0.848

AC:

14089

AN:

16608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1718

3436

5155

6873

8591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.781

AC:

118791

AN:

152036

Hom.:

47511

Cov.:

AF XY:

0.783

AC XY:

58157

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.589

AC:

24407

AN:

41422

American (AMR)

AF:

0.864

AC:

13204

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

3118

AN:

3468

East Asian (EAS)

AF:

0.810

AC:

4173

AN:

5154

South Asian (SAS)

AF:

0.877

AC:

4234

AN:

4826

European-Finnish (FIN)

AF:

0.819

AC:

8671

AN:

10588

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.856

AC:

58226

AN:

67986

Other (OTH)

AF:

0.811

AC:

1710

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1239

2478

3716

4955

6194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.807

Hom.:

11358

Bravo

AF:

0.778

Asia WGS

AF:

0.846

AC:

2941

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.2

(source)

DANN

Benign

0.52

PhyloP100

0.67

PromoterAI

-0.0034

Neutral

(source)

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