dbSNP rs1214089110: NPAS1:p.Lys35Glu (chr19-47021150-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002517.4(NPAS1):c.103A>G(p.Lys35Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,442,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

NPAS1
NM_002517.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Publications

1 publications found

Variant links:

Genes affected

NPAS1 (HGNC:7894): (neuronal PAS domain protein 1) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. Studies of a related mouse gene suggest that it functions in neurons. The exact function of this gene is unclear, but it may play protective or modulatory roles during late embryogenesis and postnatal development. [provided by RefSeq, Jul 2008]

NPAS1 links:

ENSG00000307953 (HGNC:):

ENSG00000307953 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.163097).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002517.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	NM_002517.4	MANE Select	c.103A>G	p.Lys35Glu	missense	Exon 2 of 12	NP_002508.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPAS1	ENST00000602212.6	TSL:1 MANE Select	c.103A>G	p.Lys35Glu	missense	Exon 2 of 12	ENSP00000469142.1	Q99742-1
NPAS1	ENST00000449844.6	TSL:1	c.103A>G	p.Lys35Glu	missense	Exon 1 of 11	ENSP00000405290.1	Q99742-1
NPAS1	ENST00000906441.1		c.103A>G	p.Lys35Glu	missense	Exon 2 of 12	ENSP00000576500.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000463

AC:

AN:

216062

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000762

AC:

AN:

1442698

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

717092

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31728

American (AMR)

AF:

0.00

AC:

AN:

43146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25458

East Asian (EAS)

AF:

0.00

AC:

AN:

37616

South Asian (SAS)

AF:

0.00

AC:

AN:

83980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00000996

AC:

AN:

1104084

Other (OTH)

AF:

0.00

AC:

AN:

59516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.0000471

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.54

M_CAP

Benign

0.068

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.0

PhyloP100

2.3

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.25

REVEL

Benign

0.066

Sift

Benign

0.036

Sift4G

Benign

0.34

Polyphen

0.43

Vest4

0.45

MutPred

0.23

Loss of ubiquitination at K35 (P = 0.0041)

MVP

0.17

MPC

0.95

ClinPred

0.33

GERP RS

3.0

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.18

gMVP

0.48

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over