7-24286650-T-C

Variant names:

• chr7-24286650-T-C
• rs3025120
• NM_000905.4:c.188+1222T>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+1222T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,270 control chromosomes in the GnomAD database, including 204 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 0.046 (204 hom., cov: 33)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0761 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.188+1222T>C		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.188+1222T>C		intron	N/A	ENSP00000242152.2
	NPY	ENST00000405982.1	TSL:1	c.188+1222T>C		intron	N/A	ENSP00000385282.1
	NPY	ENST00000407573.5	TSL:3	c.188+1222T>C		intron	N/A	ENSP00000384364.1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7070 AN: 152152 Hom.: 205 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0464 AC: 7072 AN: 152270 Hom.: 204 Cov.: 33 AF XY: 0.0480 AC XY: 3572 AN XY: 74458

African (AFR) AF: 0.0643 AC: 2674 AN: 41560

American (AMR) AF: 0.0273 AC: 418 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5188

South Asian (SAS) AF: 0.0828 AC: 399 AN: 4818

European-Finnish (FIN) AF: 0.0669 AC: 709 AN: 10598

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2640 AN: 68016

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

Alfa AF: 0.0410 Hom.: 195

Bravo AF: 0.0425

Asia WGS AF: 0.0580 AC: 201 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		2.0
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: rs3025120; hg19: chr7-24326269;