rs16475

Variant names:

• chr7-24291867-A-G
• rs16475
• ENST00000718234.1:n.319+27490T>C

Variant summary

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

The ENST00000718234.1(ENSG00000228944):​n.319+27490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 597,766 control chromosomes in the GnomAD database, including 1,434 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 0.053 (300 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1134 hom.)
• Consequence: ENSG00000228944 ENST00000718234.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 9 publications found

Genes affected

ENSG00000228944 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718234.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.*180A>G		downstream_gene	N/A	NP_000896.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000228944	ENST00000718234.1		n.319+27490T>C		intron	N/A
	ENSG00000228944	ENST00000745512.1		n.341+27490T>C		intron	N/A
	ENSG00000228944	ENST00000745513.1		n.309+27490T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8108 AN: 152178 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0511

GnomAD4 exome AF: 0.0683 AC: 30414 AN: 445470 Hom.: 1134 Cov.: 6 AF XY: 0.0679 AC XY: 15838 AN XY: 233414

African (AFR) AF: 0.0120 AC: 142 AN: 11816

American (AMR) AF: 0.0413 AC: 541 AN: 13102

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 592 AN: 12910

East Asian (EAS) AF: 0.0604 AC: 1741 AN: 28816

South Asian (SAS) AF: 0.0624 AC: 2199 AN: 35262

European-Finnish (FIN) AF: 0.0710 AC: 2319 AN: 32674

Middle Eastern (MID) AF: 0.0693 AC: 206 AN: 2972

European-Non Finnish (NFE) AF: 0.0748 AC: 21136 AN: 282750

Other (OTH) AF: 0.0611 AC: 1538 AN: 25168

GnomAD4 genome AF: 0.0532 AC: 8108 AN: 152296 Hom.: 300 Cov.: 32 AF XY: 0.0534 AC XY: 3977 AN XY: 74458

African (AFR) AF: 0.0126 AC: 524 AN: 41564

American (AMR) AF: 0.0455 AC: 697 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5182

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4828

European-Finnish (FIN) AF: 0.0738 AC: 782 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5254 AN: 68028

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0638 Hom.: 99

Bravo AF: 0.0478

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.0
DANN	Benign	0.86
PhyloP100		0.0020
Mutation Taster		=94/6	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16475; hg19: chr7-24331486;