chr7-24285140-T-G

Variant names:

• chr7-24285140-T-G
• rs16141
• ENST00000405982.1:c.-101T>G

Variant summary

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

The ENST00000405982.1(NPY):​c.-101T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,201,848 control chromosomes in the GnomAD database, including 157,119 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 0.48 (17969 hom., cov: 31)
  • Exomes 𝑓: 0.51 (139150 hom.)
• Consequence: NPY ENST00000405982.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 11 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 = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405982.1. 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.1-101T>G		intron	N/A	NP_000896.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000405982.1	TSL:1	c.-101T>G		5_prime_UTR	Exon 1 of 3	ENSP00000385282.1
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.1-101T>G		intron	N/A	ENSP00000242152.2
	NPY	ENST00000407573.5	TSL:3	c.-1+64T>G		intron	N/A	ENSP00000384364.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72788 AN: 151720 Hom.: 17964 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.511 AC: 536177 AN: 1050010 Hom.: 139150 Cov.: 14 AF XY: 0.510 AC XY: 272124 AN XY: 533568

African (AFR) AF: 0.380 AC: 9816 AN: 25842

American (AMR) AF: 0.675 AC: 28657 AN: 42434

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 12023 AN: 21172

East Asian (EAS) AF: 0.669 AC: 25230 AN: 37720

South Asian (SAS) AF: 0.516 AC: 36523 AN: 70840

European-Finnish (FIN) AF: 0.523 AC: 23966 AN: 45786

Middle Eastern (MID) AF: 0.473 AC: 2013 AN: 4260

European-Non Finnish (NFE) AF: 0.496 AC: 374392 AN: 755198

Other (OTH) AF: 0.504 AC: 23557 AN: 46758

GnomAD4 genome AF: 0.480 AC: 72825 AN: 151838 Hom.: 17969 Cov.: 31 AF XY: 0.486 AC XY: 36028 AN XY: 74200

African (AFR) AF: 0.375 AC: 15527 AN: 41394

American (AMR) AF: 0.586 AC: 8961 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3443 AN: 5142

South Asian (SAS) AF: 0.531 AC: 2549 AN: 4798

European-Finnish (FIN) AF: 0.511 AC: 5378 AN: 10528

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33480 AN: 67914

Other (OTH) AF: 0.483 AC: 1016 AN: 2104

Alfa AF: 0.479 Hom.: 18021

Bravo AF: 0.481

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.46
PhyloP100		-0.022
PromoterAI		0.0065	Neutral
Mutation Taster		=297/3	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: rs16141; hg19: chr7-24324759;