rs16478

chr7-24284989-G-Achr7-24284989-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC107986777 (HGNC:):

ACMG classification

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/exons	MANE	UniProt
NPY	NM_000905.4	c.1-252G>A		intron_variant		ENST00000242152.7
LOC107986777	XR_001745132.2	n.209+34368C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY	ENST00000242152.7	c.1-252G>A		intron_variant		1	NM_000905.4	P1
NPY	ENST00000407573.5	c.-88G>A		5_prime_UTR_variant	2/5	3		P1

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

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.: 33 AF XY: 0.278 AC XY: 20662 AN XY: 74364

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

Other links and lift over

dbSNP: rs16478; hg19: chr7-24324608;