NM_001164749.2:c.853-10771C>T

Variant summary

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

The NM_001164749.2(NPAS3):​c.853-10771C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,186 control chromosomes in the GnomAD database, including 1,740 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 0.14 ( 1740 hom., cov: 33)

Consequence

NPAS3
NM_001164749.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

1 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]

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=-0.83).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPAS3NM_001164749.2 linkc.853-10771C>T intron_variant Intron 7 of 11 ENST00000356141.9 NP_001158221.1 Q8IXF0-1X5D2Q4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPAS3ENST00000356141.9 linkc.853-10771C>T intron_variant Intron 7 of 11 1 NM_001164749.2 ENSP00000348460.4 Q8IXF0-1

Frequencies

GnomAD3 genomes
AF:
0.135
AC:
20555
AN:
152068
Hom.:
1735
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.229
Gnomad AMI
AF:
0.135
Gnomad AMR
AF:
0.104
Gnomad ASJ
AF:
0.0878
Gnomad EAS
AF:
0.0325
Gnomad SAS
AF:
0.0967
Gnomad FIN
AF:
0.0955
Gnomad MID
AF:
0.139
Gnomad NFE
AF:
0.104
Gnomad OTH
AF:
0.139
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.135
AC:
20589
AN:
152186
Hom.:
1740
Cov.:
33
AF XY:
0.132
AC XY:
9839
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.229
AC:
9498
AN:
41494
American (AMR)
AF:
0.104
AC:
1590
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.0878
AC:
305
AN:
3472
East Asian (EAS)
AF:
0.0322
AC:
166
AN:
5160
South Asian (SAS)
AF:
0.0961
AC:
463
AN:
4816
European-Finnish (FIN)
AF:
0.0955
AC:
1013
AN:
10608
Middle Eastern (MID)
AF:
0.133
AC:
39
AN:
294
European-Non Finnish (NFE)
AF:
0.104
AC:
7088
AN:
68012
Other (OTH)
AF:
0.144
AC:
304
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
909
1818
2727
3636
4545
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
220
440
660
880
1100
<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:
0.114
Hom.:
1892
Bravo
AF:
0.140
Asia WGS
AF:
0.102
AC:
354
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.4
DANN
Benign
0.78
PhyloP100
-1.2
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs17101861; hg19: chr14-34232772; API