4-163343624-A-G

Variant names:

• chr4-163343624-A-G
• rs4314240
• ENST00000919917.1:c.-2378A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000919917.1(NPY5R):​c.-2378A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,036 control chromosomes in the GnomAD database, including 58,333 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 0.87 (58333 hom., cov: 30)
• Consequence: NPY5R ENST00000919917.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 3 publications found

Genes affected

NPY5R (HGNC:7958): (neuropeptide Y receptor Y5) The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

NPY1R (HGNC:7956): (neuropeptide Y receptor Y1) This gene belongs to the G-protein-coupled receptor superfamily. The encoded transmembrane protein mediates the function of neuropeptide Y (NPY), a neurotransmitter, and peptide YY (PYY), a gastrointestinal hormone. The encoded receptor undergoes fast agonist-induced internalization through clathrin-coated pits and is subsequently recycled back to the cell membrane. Activation of Y1 receptors may result in mobilization of intracellular calcium and inhibition of adenylate cyclase activity. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000919917.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY5R	ENST00000919917.1		c.-2378A>G		5_prime_UTR	Exon 1 of 5	ENSP00000589976.1
	NPY1R	ENST00000967840.1		c.-152+1150T>C		intron	N/A	ENSP00000637899.1
	NPY1R	ENST00000511901.1	TSL:3	c.-152+681T>C		intron	N/A	ENSP00000423878.1	D6RC44

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132851 AN: 151918 Hom.: 58294 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.874 AC: 132943 AN: 152036 Hom.: 58333 Cov.: 30 AF XY: 0.869 AC XY: 64575 AN XY: 74318

African (AFR) AF: 0.887 AC: 36763 AN: 41468

American (AMR) AF: 0.809 AC: 12370 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2924 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3573 AN: 5116

South Asian (SAS) AF: 0.781 AC: 3748 AN: 4796

European-Finnish (FIN) AF: 0.871 AC: 9222 AN: 10592

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61349 AN: 67994

Other (OTH) AF: 0.883 AC: 1861 AN: 2108

Alfa AF: 0.889 Hom.: 73446

Bravo AF: 0.870

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.54
PhyloP100		0.079
PromoterAI		0.0048	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4314240; hg19: chr4-164264776;