Genetic Variant NPY:c.-52C>G (chr7-24285189-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000405982.1(NPY):c.-52C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,586,338 control chromosomes in the GnomAD database, including 57,403 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 0.28 ( 6254 hom., cov: 31)

Exomes 𝑓: 0.26 ( 51149 hom. )

Consequence

NPY
ENST00000405982.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

12 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4 link	c.1-52C>G		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.1-52C>G		intron_variant	Intron 1 of 3	1	NM_000905.4	ENSP00000242152.2		P01303

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43043

AN:

151796

Hom.:

6247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.293

GnomAD4 exome

AF:

0.264

AC:

378638

AN:

1434424

Hom.:

51149

Cov.:

AF XY:

0.266

AC XY:

190413

AN XY:

714866

show subpopulations

African (AFR)

AF:

0.342

AC:

11281

AN:

32998

American (AMR)

AF:

0.184

AC:

8214

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6724

AN:

25736

East Asian (EAS)

AF:

0.284

AC:

11227

AN:

39556

South Asian (SAS)

AF:

0.310

AC:

26490

AN:

85410

European-Finnish (FIN)

AF:

0.241

AC:

12743

AN:

52816

Middle Eastern (MID)

AF:

0.347

AC:

1962

AN:

5652

European-Non Finnish (NFE)

AF:

0.261

AC:

283825

AN:

1088274

Other (OTH)

AF:

0.272

AC:

16172

AN:

59432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

14040

28080

42119

56159

70199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9488

18976

28464

37952

47440

<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:

0.284

AC:

43072

AN:

151914

Hom.:

6254

Cov.:

AF XY:

0.282

AC XY:

20951

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.340

AC:

14092

AN:

41426

American (AMR)

AF:

0.225

AC:

3433

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

916

AN:

3472

East Asian (EAS)

AF:

0.280

AC:

1439

AN:

5142

South Asian (SAS)

AF:

0.310

AC:

1487

AN:

4802

European-Finnish (FIN)

AF:

0.253

AC:

2668

AN:

10552

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17949

AN:

67938

Other (OTH)

AF:

0.292

AC:

615

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1558

3116

4673

6231

7789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.144

Hom.:

266

Bravo

AF:

0.284

Asia WGS

AF:

0.286

AC:

994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.78

(source)

DANN

Benign

0.55

PhyloP100

-1.4

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=100/0

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