rs3779477

Positions:

• chr7-24287907-G-A
• chr7-24287907-G-C

Variant summary

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

The NM_000905.4(NPY):​c.189-1592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,982 control chromosomes in the GnomAD database, including 13,587 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 0.42 (13587 hom., cov: 31)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY	NM_000905.4	c.189-1592G>A		intron_variant		ENST00000242152.7
LOC107986777	XR_001745132.2	n.209+31450C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY	ENST00000242152.7	c.189-1592G>A		intron_variant		1	NM_000905.4	P1
NPY	ENST00000405982.1	c.189-1592G>A		intron_variant		1		P1
NPY	ENST00000407573.5	c.189-1592G>A		intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63425 AN: 151864 Hom.: 13588 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.417 AC: 63444 AN: 151982 Hom.: 13587 Cov.: 31 AF XY: 0.413 AC XY: 30691 AN XY: 74292

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.418

Alfa AF: 0.460 Hom.: 23437

Bravo AF: 0.411

Asia WGS AF: 0.254 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.34

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: rs3779477; hg19: chr7-24327526; COSMIC: COSV54215838;