chr7-24284969-C-T

Variant names:

• chr7-24284969-C-T
• rs16143
• NM_000905.4:c.1-272C>T

Variant summary

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

The NM_000905.4(NPY):​c.1-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 547,464 control chromosomes in the GnomAD database, including 21,115 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 0.29 (6964 hom., cov: 32)
  • Exomes 𝑓: 0.26 (14151 hom.)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4	c.1-272C>T		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	ENST00000242152.7	c.1-272C>T		intron_variant	Intron 1 of 3	1	NM_000905.4	ENSP00000242152.2
NPY	ENST00000407573	c.-108C>T		5_prime_UTR_variant	Exon 2 of 5	3		ENSP00000384364.1
NPY	ENST00000405982.1	c.-272C>T		upstream_gene_variant		1		ENSP00000385282.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44824 AN: 152006 Hom.: 6952 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.262 AC: 103569 AN: 395340 Hom.: 14151 Cov.: 2 AF XY: 0.263 AC XY: 54552 AN XY: 207188

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.295 AC: 44873 AN: 152124 Hom.: 6964 Cov.: 32 AF XY: 0.293 AC XY: 21799 AN XY: 74366

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.301

Alfa AF: 0.275 Hom.: 771

Bravo AF: 0.296

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.80

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: rs16143; hg19: chr7-24324588;