rs16135

Positions:

• chr7-24288301-A-G
• chr7-24288301-A-T

Variant summary

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

The NM_000905.4(NPY):​c.189-1198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,254 control chromosomes in the GnomAD database, including 62,170 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 0.90 (62170 hom., cov: 32)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY	NM_000905.4	c.189-1198A>G		intron_variant		ENST00000242152.7	NP_000896.1
LOC107986777	XR_001745132.2	n.209+31056T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.189-1198A>G		intron_variant		1	NM_000905.4	ENSP00000242152	P1
NPY	ENST00000405982.1	c.189-1198A>G		intron_variant		1		ENSP00000385282	P1
NPY	ENST00000407573.5	c.189-1198A>G		intron_variant		3		ENSP00000384364	P1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137142 AN: 152136 Hom.: 62144 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.901 AC: 137222 AN: 152254 Hom.: 62170 Cov.: 32 AF XY: 0.894 AC XY: 66576 AN XY: 74442

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.899

Alfa AF: 0.897 Hom.: 23545

Bravo AF: 0.897

Asia WGS AF: 0.735 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs16135; hg19: chr7-24327920;