dbSNP rs16478: NPY:c.1-252G>A (chr7-24284989-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000905.4(NPY):c.1-252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 568,054 control chromosomes in the GnomAD database, including 20,753 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 ( 6124 hom., cov: 33)

Exomes 𝑓: 0.26 ( 14629 hom. )

Consequence

NPY
NM_000905.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.921

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:

LOC107986777 (HGNC:):

LOC107986777 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 (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4 link	c.1-252G>A		intron_variant	Intron 1 of 3	ENST00000242152.7	NP_000896.1	P01303A4D158

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPY	ENST00000242152.7 link	c.1-252G>A	intron_variant	Intron 1 of 3	1	NM_000905.4	ENSP00000242152.2	P01303
NPY	ENST00000407573 link	c.-88G>A	5_prime_UTR_variant	Exon 2 of 5	3		ENSP00000384364.1	P01303
NPY	ENST00000405982.1 link	c.-252G>A	upstream_gene_variant		1		ENSP00000385282.1	P01303

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42462

AN:

152002

Hom.:

6117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.261

AC:

108371

AN:

415934

Hom.:

14629

Cov.:

AF XY:

0.262

AC XY:

57213

AN XY:

218158

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.279

AC:

42491

AN:

152120

Hom.:

6124

Cov.:

AF XY:

0.278

AC XY:

20662

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.259

Hom.:

8732

Bravo

AF:

0.279

Asia WGS

AF:

0.296

AC:

1027

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.2

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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