rs16139

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000905.4(NPY):c.20T>C(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 1,614,018 control chromosomes in the GnomAD database, including 1,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 85 hom., cov: 32)

Exomes 𝑓: 0.034 ( 960 hom. )

Consequence

NPY
NM_000905.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.31

Publications

178 publications found

Variant links:

Genes affected

NPY (HGNC:7955): (neuropeptide Y) This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]

NPY links:

ENSG00000228944 (HGNC:):

ENSG00000228944 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022782385).

BP6

Variant 7-24285260-T-C is Benign according to our data. Variant chr7-24285260-T-C is described in ClinVar as Benign. ClinVar VariationId is 14024.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0272 (4144/152250) while in subpopulation NFE AF = 0.0383 (2602/68012). AF 95% confidence interval is 0.037. There are 85 homozygotes in GnomAd4. There are 2105 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4144 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000905.4. 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
	NPY	NM_000905.4	MANE Select	c.20T>C	p.Leu7Pro	missense	Exon 2 of 4	NP_000896.1	P01303

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPY	ENST00000242152.7	TSL:1 MANE Select	c.20T>C	p.Leu7Pro	missense	Exon 2 of 4	ENSP00000242152.2	P01303
NPY	ENST00000405982.1	TSL:1	c.20T>C	p.Leu7Pro	missense	Exon 1 of 3	ENSP00000385282.1	P01303
NPY	ENST00000407573.5	TSL:3	c.20T>C	p.Leu7Pro	missense	Exon 3 of 5	ENSP00000384364.1	P01303

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4146

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00630

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0326

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0278

GnomAD2 exomes

AF:

0.0298

AC:

7467

AN:

250628

AF XY:

0.0310

show subpopulations

Gnomad AFR exome

AF:

0.00696

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0629

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0378

GnomAD4 exome

AF:

0.0338

AC:

49382

AN:

1461768

Hom.:

960

Cov.:

AF XY:

0.0338

AC XY:

24547

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00520

AC:

174

AN:

33476

American (AMR)

AF:

0.0167

AC:

746

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

279

AN:

26128

East Asian (EAS)

AF:

0.000176

AC:

AN:

39696

South Asian (SAS)

AF:

0.0323

AC:

2782

AN:

86252

European-Finnish (FIN)

AF:

0.0663

AC:

3541

AN:

53396

Middle Eastern (MID)

AF:

0.0274

AC:

158

AN:

5766

European-Non Finnish (NFE)

AF:

0.0358

AC:

39766

AN:

1111942

Other (OTH)

AF:

0.0319

AC:

1929

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2685

5370

8055

10740

13425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1398

2796

4194

5592

6990

<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:

0.0272

AC:

4144

AN:

152250

Hom.:

Cov.:

AF XY:

0.0283

AC XY:

2105

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00628

AC:

261

AN:

41548

American (AMR)

AF:

0.0208

AC:

319

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.0324

AC:

156

AN:

4816

European-Finnish (FIN)

AF:

0.0643

AC:

683

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0383

AC:

2602

AN:

68012

Other (OTH)

AF:

0.0275

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

205

410

614

819

1024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0319

Hom.:

363

Bravo

AF:

0.0219

TwinsUK

AF:

0.0313

AC:

116

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.0362

AC:

311

ExAC

AF:

0.0302

AC:

3670

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0312

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

NPY POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.017

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

PhyloP100

3.3

PrimateAI

Uncertain

0.48

PROVEAN

Benign

1.8

REVEL

Benign

0.084

Sift

Benign

0.16

Sift4G

Uncertain

0.060

Polyphen

0.0

Vest4

0.42

MPC

2.0

ClinPred

0.029

GERP RS

5.6

PromoterAI

0.0024

Neutral

(source)

Varity_R

0.37

gMVP

0.56

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over