chr7-24288301-A-G

Variant names:

• chr7-24288301-A-G
• rs16135
• NM_000905.4:c.189-1198A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 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.189-1198A>G		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.189-1198A>G		intron	N/A	ENSP00000242152.2
	NPY	ENST00000405982.1	TSL:1	c.189-1198A>G		intron	N/A	ENSP00000385282.1
	NPY	ENST00000407573.5	TSL:3	c.189-1198A>G		intron	N/A	ENSP00000384364.1

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

African (AFR) AF: 0.937 AC: 38898 AN: 41532

American (AMR) AF: 0.798 AC: 12202 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3136 AN: 3472

East Asian (EAS) AF: 0.699 AC: 3625 AN: 5186

South Asian (SAS) AF: 0.806 AC: 3887 AN: 4820

European-Finnish (FIN) AF: 0.896 AC: 9509 AN: 10608

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62894 AN: 68026

Other (OTH) AF: 0.899 AC: 1900 AN: 2114

Alfa AF: 0.901 Hom.: 28483

Bravo AF: 0.897

Asia WGS AF: 0.735 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.14
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: rs16135; hg19: chr7-24327920;