rs16132

Variant names:

• chr7-24289901-T-A
• rs16132
• NM_000905.4:c.269+322T>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.269+322T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 152,014 control chromosomes in the GnomAD database, including 703 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 0.057 (703 hom., cov: 31)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 0 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4	c.269+322T>A		intron_variant	Intron 3 of 3	ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.269+322T>A		intron_variant	Intron 3 of 3	1	NM_000905.4	ENSP00000242152.2

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8583 AN: 151896 Hom.: 703 Cov.: 31

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0624

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0566 AC: 8597 AN: 152014 Hom.: 703 Cov.: 31 AF XY: 0.0643 AC XY: 4778 AN XY: 74296

African (AFR) AF: 0.0132 AC: 546 AN: 41474

American (AMR) AF: 0.174 AC: 2654 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1545 AN: 5148

South Asian (SAS) AF: 0.180 AC: 866 AN: 4800

European-Finnish (FIN) AF: 0.0523 AC: 553 AN: 10568

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0303 AC: 2059 AN: 67972

Other (OTH) AF: 0.0641 AC: 135 AN: 2106

Alfa AF: 0.0417 Hom.: 36

Bravo AF: 0.0626

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16132; hg19: chr7-24329520;