chr7-24287907-G-A

Variant names:

• chr7-24287907-G-A
• rs3779477
• NM_000905.4:c.189-1592G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000905.4. 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.189-1592G>A		intron	N/A	NP_000896.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.189-1592G>A		intron	N/A	ENSP00000242152.2
	NPY	ENST00000405982.1	TSL:1	c.189-1592G>A		intron	N/A	ENSP00000385282.1
	NPY	ENST00000407573.5	TSL:3	c.189-1592G>A		intron	N/A	ENSP00000384364.1

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

African (AFR) AF: 0.347 AC: 14395 AN: 41460

American (AMR) AF: 0.399 AC: 6086 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1693 AN: 3464

East Asian (EAS) AF: 0.238 AC: 1230 AN: 5164

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4816

European-Finnish (FIN) AF: 0.458 AC: 4832 AN: 10544

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

European-Non Finnish (NFE) AF: 0.473 AC: 32166 AN: 67952

Other (OTH) AF: 0.418 AC: 882 AN: 2108

Alfa AF: 0.448 Hom.: 37392

Bravo AF: 0.411

Asia WGS AF: 0.254 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.34
PhyloP100		-1.1
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: rs3779477; hg19: chr7-24327526; COSMIC: COSV54215838;