Variant rs2305160 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002518.4(NPAS2):c.1180A>G(p.Thr394Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,613,724 control chromosomes in the GnomAD database, including 380,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.74 ( 42959 hom., cov: 33)

Exomes 𝑓: 0.68 ( 337144 hom. )

Consequence

NPAS2
NM_002518.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.590

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-AS1 (HGNC:40408): (NPAS2 antisense RNA 1)

NPAS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0232136E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4 linkuse as main transcript	c.1180A>G	p.Thr394Ala	missense_variant	13/21	ENST00000335681.10
NPAS2-AS1	NR_110213.1 linkuse as main transcript	n.575+443T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10 linkuse as main transcript	c.1180A>G	p.Thr394Ala	missense_variant	13/21	1	NM_002518.4	P1
NPAS2-AS1	ENST00000652285.1 linkuse as main transcript	n.605+443T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113038

AN:

151992

Hom.:

42911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.729

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.839

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.725

GnomAD3 exomes

AF:

0.707

AC:

177742

AN:

251262

Hom.:

63648

AF XY:

0.702

AC XY:

95266

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.902

Gnomad AMR exome

AF:

0.708

Gnomad ASJ exome

AF:

0.670

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.690

GnomAD4 exome

AF:

0.676

AC:

988604

AN:

1461614

Hom.:

337144

Cov.:

AF XY:

0.676

AC XY:

491746

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.906

Gnomad4 AMR exome

AF:

0.711

Gnomad4 ASJ exome

AF:

0.669

Gnomad4 EAS exome

AF:

0.830

Gnomad4 SAS exome

AF:

0.711

Gnomad4 FIN exome

AF:

0.716

Gnomad4 NFE exome

AF:

0.657

Gnomad4 OTH exome

AF:

0.696

GnomAD4 genome

AF:

0.744

AC:

113143

AN:

152110

Hom.:

42959

Cov.:

AF XY:

0.748

AC XY:

55597

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.898

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.659

Gnomad4 EAS

AF:

0.839

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.729

Gnomad4 NFE

AF:

0.654

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.677

Hom.:

90032

Bravo

AF:

0.751

TwinsUK

AF:

0.648

AC:

2403

ALSPAC

AF:

0.663

AC:

2556

ESP6500AA

AF:

0.893

AC:

3934

ESP6500EA

AF:

0.673

AC:

5788

ExAC

AF:

0.707

AC:

85827

Asia WGS

AF:

0.800

AC:

2782

AN:

3478

EpiCase

AF:

0.668

EpiControl

AF:

0.666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.13

DANN

Benign

0.41

DEOGEN2

Benign

0.041

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.029

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.075

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.34

REVEL

Benign

0.013

Sift

Benign

0.85

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.026

MPC

0.28

ClinPred

0.00058

GERP RS

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.013

gMVP

0.31

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