7-24285876-G-C

Variant names:

• chr7-24285876-G-C
• rs16138
• NM_000905.4:c.188+448G>C

Variant summary

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

The NM_000905.4(NPY):​c.188+448G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,024 control chromosomes in the GnomAD database, including 7,660 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 0.31 (7660 hom., cov: 32)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.188+448G>C		intron	N/A	NP_000896.1	P01303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.188+448G>C		intron	N/A	ENSP00000242152.2	P01303
	NPY	ENST00000405982.1	TSL:1	c.188+448G>C		intron	N/A	ENSP00000385282.1	P01303
	NPY	ENST00000407573.5	TSL:3	c.188+448G>C		intron	N/A	ENSP00000384364.1	P01303

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46607 AN: 151906 Hom.: 7641 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.307 AC: 46666 AN: 152024 Hom.: 7660 Cov.: 32 AF XY: 0.304 AC XY: 22603 AN XY: 74294

African (AFR) AF: 0.430 AC: 17825 AN: 41464

American (AMR) AF: 0.235 AC: 3596 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2667 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17690 AN: 67950

Other (OTH) AF: 0.308 AC: 650 AN: 2110

Alfa AF: 0.166 Hom.: 330

Bravo AF: 0.310

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.41
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: rs16138; hg19: chr7-24325495;