NM_000905.4:c.1-252G>A

Variant names:

• chr7-24284989-G-A
• rs16478
• NM_000905.4:c.1-252G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 9 publications found

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]

ENSG00000228944 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.1-252G>A		intron	N/A	NP_000896.1	P01303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.1-252G>A		intron	N/A	ENSP00000242152.2	P01303
	NPY	ENST00000407573.5	TSL:3	c.-88G>A		5_prime_UTR	Exon 2 of 5	ENSP00000384364.1	P01303
	NPY	ENST00000925261.1		c.-88G>A		5_prime_UTR	Exon 1 of 4	ENSP00000595320.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42462 AN: 152002 Hom.: 6117 Cov.: 33

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.: 3 AF XY: 0.262 AC XY: 57213 AN XY: 218158

African (AFR) AF: 0.343 AC: 3931 AN: 11458

American (AMR) AF: 0.196 AC: 3284 AN: 16792

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 3070 AN: 12842

East Asian (EAS) AF: 0.280 AC: 7882 AN: 28192

South Asian (SAS) AF: 0.290 AC: 12589 AN: 43356

European-Finnish (FIN) AF: 0.231 AC: 6356 AN: 27522

Middle Eastern (MID) AF: 0.330 AC: 607 AN: 1840

European-Non Finnish (NFE) AF: 0.257 AC: 64167 AN: 249656

Other (OTH) AF: 0.267 AC: 6485 AN: 24276

GnomAD4 genome AF: 0.279 AC: 42491 AN: 152120 Hom.: 6124 Cov.: 33 AF XY: 0.278 AC XY: 20662 AN XY: 74364

African (AFR) AF: 0.343 AC: 14221 AN: 41488

American (AMR) AF: 0.221 AC: 3381 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 852 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1438 AN: 5160

South Asian (SAS) AF: 0.298 AC: 1437 AN: 4830

European-Finnish (FIN) AF: 0.252 AC: 2665 AN: 10584

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17443 AN: 67988

Other (OTH) AF: 0.283 AC: 599 AN: 2116

Alfa AF: 0.260 Hom.: 13118

Bravo AF: 0.279

Asia WGS AF: 0.296 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.87
PhyloP100		-0.92
PromoterAI		-0.0034	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16478; hg19: chr7-24324608;