7-24285051-A-G

Position:

• chr7-24285051-A-G

Variant summary

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

The NM_000905.4(NPY):​c.1-190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 621,746 control chromosomes in the GnomAD database, including 25,406 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 (7889 hom., cov: 32)
  • Exomes 𝑓: 0.27 (17517 hom.)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY	NM_000905.4	c.1-190A>G		intron_variant		ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.1-190A>G		intron_variant		1	NM_000905.4	ENSP00000242152.2
NPY	ENST00000407573.5	c.-26A>G		5_prime_UTR_variant	2/5	3		ENSP00000384364.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47051 AN: 151812 Hom.: 7869 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.268 AC: 125716 AN: 469816 Hom.: 17517 Cov.: 5 AF XY: 0.270 AC XY: 66524 AN XY: 246842

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.310 AC: 47110 AN: 151930 Hom.: 7889 Cov.: 32 AF XY: 0.308 AC XY: 22884 AN XY: 74290

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.311

Alfa AF: 0.284 Hom.: 839

Bravo AF: 0.313

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs16142; hg19: chr7-24324670; COSMIC: COSV54215563; COSMIC: COSV54215563;