7-24285189-C-G

Variant names:

• chr7-24285189-C-G
• rs16140
• ENST00000405982.1:c.-52C>G

Variant summary

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

The ENST00000405982.1(NPY):​c.-52C>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 0.266 in 1,586,338 control chromosomes in the GnomAD database, including 57,403 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 (6254 hom., cov: 31)
  • Exomes 𝑓: 0.26 (51149 hom.)
• Consequence: NPY ENST00000405982.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.1-52C>G		intron	N/A	NP_000896.1	P01303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000405982.1	TSL:1	c.-52C>G		5_prime_UTR	Exon 1 of 3	ENSP00000385282.1	P01303
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.1-52C>G		intron	N/A	ENSP00000242152.2	P01303
	NPY	ENST00000925262.1		c.-52C>G		5_prime_UTR	Exon 1 of 2	ENSP00000595321.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43043 AN: 151796 Hom.: 6247 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.264 AC: 378638 AN: 1434424 Hom.: 51149 Cov.: 27 AF XY: 0.266 AC XY: 190413 AN XY: 714866

African (AFR) AF: 0.342 AC: 11281 AN: 32998

American (AMR) AF: 0.184 AC: 8214 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6724 AN: 25736

East Asian (EAS) AF: 0.284 AC: 11227 AN: 39556

South Asian (SAS) AF: 0.310 AC: 26490 AN: 85410

European-Finnish (FIN) AF: 0.241 AC: 12743 AN: 52816

Middle Eastern (MID) AF: 0.347 AC: 1962 AN: 5652

European-Non Finnish (NFE) AF: 0.261 AC: 283825 AN: 1088274

Other (OTH) AF: 0.272 AC: 16172 AN: 59432

GnomAD4 genome AF: 0.284 AC: 43072 AN: 151914 Hom.: 6254 Cov.: 31 AF XY: 0.282 AC XY: 20951 AN XY: 74204

African (AFR) AF: 0.340 AC: 14092 AN: 41426

American (AMR) AF: 0.225 AC: 3433 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1439 AN: 5142

South Asian (SAS) AF: 0.310 AC: 1487 AN: 4802

European-Finnish (FIN) AF: 0.253 AC: 2668 AN: 10552

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17949 AN: 67938

Other (OTH) AF: 0.292 AC: 615 AN: 2104

Alfa AF: 0.144 Hom.: 266

Bravo AF: 0.284

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.55
PhyloP100		-1.4
PromoterAI		0.012	Neutral
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: rs16140; hg19: chr7-24324808; COSMIC: COSV54216152;