Variant rs1562313 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002518.4(NPAS2):c.1059C>T(p.Tyr353Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,612,266 control chromosomes in the GnomAD database, including 35,570 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 0.22 ( 3736 hom., cov: 32)

Exomes 𝑓: 0.21 ( 31834 hom. )

Consequence

NPAS2
NM_002518.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

NPAS2 (HGNC:7895): (neuronal PAS domain protein 2) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. A similar mouse protein may play a regulatory role in the acquisition of specific types of memory. It also may function as a part of a molecular clock operative in the mammalian forebrain. [provided by RefSeq, Jul 2008]

NPAS2 links:

NPAS2 (HGNC:):

NPAS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4 linkuse as main transcript	c.1059C>T	p.Tyr353Tyr	synonymous_variant	12/21	ENST00000335681.10	NP_002509.2	Q99743A2I2P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NPAS2	ENST00000335681.10 linkuse as main transcript	c.1059C>T	p.Tyr353Tyr	synonymous_variant	12/21	1	NM_002518.4	ENSP00000338283.5	Q99743
NPAS2	ENST00000474550.5 linkuse as main transcript	n.393C>T		non_coding_transcript_exon_variant	1/9	1
NPAS2	ENST00000448812.5 linkuse as main transcript	c.717C>T	p.Tyr239Tyr	synonymous_variant	7/7	5		ENSP00000388528.1	H7BZA3
NPAS2-AS1	ENST00000652285.1 linkuse as main transcript	n.945G>A		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32972

AN:

151848

Hom.:

3731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.193

AC:

48427

AN:

251312

Hom.:

5088

AF XY:

0.194

AC XY:

26331

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.0814

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.206

AC:

300790

AN:

1460300

Hom.:

31834

Cov.:

AF XY:

0.206

AC XY:

149586

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.0876

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.217

AC:

33000

AN:

151966

Hom.:

3736

Cov.:

AF XY:

0.215

AC XY:

16007

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.199

Hom.:

7419

Bravo

AF:

0.212

Asia WGS

AF:

0.245

AC:

849

AN:

3478

EpiCase

AF:

0.197

EpiControl

AF:

0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.70

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over