chr7-24285189-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405982(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 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4	c.1-52C>G		intron_variant	Intron 1 of 3	ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000405982	c.-52C>G		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000385282.1
NPY	ENST00000242152.7	c.1-52C>G		intron_variant	Intron 1 of 3	1	NM_000905.4	ENSP00000242152.2
NPY	ENST00000407573.5	c.1-52C>G		intron_variant	Intron 2 of 4	3		ENSP00000384364.1

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

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.272

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.292

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs16140; hg19: chr7-24324808; COSMIC: COSV54216152;