dbSNP rs16143: NPY:c.1-272C>T (chr7-24284969-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000905.4(NPY):c.1-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 547,464 control chromosomes in the GnomAD database, including 21,115 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 0.29 ( 6964 hom., cov: 32)

Exomes 𝑓: 0.26 ( 14151 hom. )

Consequence

NPY
NM_000905.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4 link	c.1-272C>T		intron_variant	Intron 1 of 3	ENST00000242152.7	NP_000896.1	P01303A4D158

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7 link	c.1-272C>T		intron_variant	Intron 1 of 3	1	NM_000905.4	ENSP00000242152.2		P01303

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44824

AN:

152006

Hom.:

6952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.302

GnomAD4 exome

AF:

0.262

AC:

103569

AN:

395340

Hom.:

14151

Cov.:

AF XY:

0.263

AC XY:

54552

AN XY:

207188

show subpopulations

African (AFR)

AF:

0.391

AC:

4248

AN:

10870

American (AMR)

AF:

0.201

AC:

3184

AN:

15842

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

2949

AN:

12272

East Asian (EAS)

AF:

0.278

AC:

7296

AN:

26256

South Asian (SAS)

AF:

0.289

AC:

12125

AN:

41988

European-Finnish (FIN)

AF:

0.230

AC:

5955

AN:

25938

Middle Eastern (MID)

AF:

0.327

AC:

568

AN:

1736

European-Non Finnish (NFE)

AF:

0.257

AC:

60943

AN:

237338

Other (OTH)

AF:

0.273

AC:

6301

AN:

23100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3367

6734

10102

13469

16836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.295

AC:

44873

AN:

152124

Hom.:

6964

Cov.:

AF XY:

0.293

AC XY:

21799

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.395

AC:

16393

AN:

41488

American (AMR)

AF:

0.230

AC:

3518

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

852

AN:

3472

East Asian (EAS)

AF:

0.278

AC:

1434

AN:

5154

South Asian (SAS)

AF:

0.299

AC:

1440

AN:

4824

European-Finnish (FIN)

AF:

0.252

AC:

2665

AN:

10586

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17474

AN:

67986

Other (OTH)

AF:

0.301

AC:

636

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1620

3240

4859

6479

8099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.275

Hom.:

771

Bravo

AF:

0.296

Asia WGS

AF:

0.299

AC:

1040

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.6

(source)

DANN

Benign

0.80

PhyloP100

-0.023

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over