rs16475

Positions:

• chr7-24291867-A-G

Variant summary

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

The XR_001745132.2(LOC107986777):​n.209+27490T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 597,766 control chromosomes in the GnomAD database, including 1,434 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 0.053 (300 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1134 hom.)
• Consequence: LOC107986777 XR_001745132.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

Genes affected

LOC107986777 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107986777	XR_001745132.2	n.209+27490T>C		intron_variant, non_coding_transcript_variant
NPY	NM_000905.4			downstream_gene_variant		ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7			downstream_gene_variant		1	NM_000905.4	ENSP00000242152	P1
NPY	ENST00000405982.1			downstream_gene_variant		1		ENSP00000385282	P1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8108 AN: 152178 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0511

GnomAD4 exome AF: 0.0683 AC: 30414 AN: 445470 Hom.: 1134 Cov.: 6 AF XY: 0.0679 AC XY: 15838 AN XY: 233414

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0413

Gnomad4 ASJ exome AF: 0.0459

Gnomad4 EAS exome AF: 0.0604

Gnomad4 SAS exome AF: 0.0624

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.0748

Gnomad4 OTH exome AF: 0.0611

GnomAD4 genome AF: 0.0532 AC: 8108 AN: 152296 Hom.: 300 Cov.: 32 AF XY: 0.0534 AC XY: 3977 AN XY: 74458

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.0336

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0640 Hom.: 52

Bravo AF: 0.0478

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.0
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16475; hg19: chr7-24331486;