4-163343624-A-G

Variant names:

• chr4-163343624-A-G
• rs4314240
• ENST00000511901.1:c.-152+681T>C

Variant summary

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

The ENST00000511901.1(NPY1R):​c.-152+681T>C variant causes a intron 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: NPY1R ENST00000511901.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 3 publications found

Genes affected

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY1R	XM_005263031.5	c.-152+681T>C		intron_variant	Intron 1 of 2		XP_005263088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000511901.1	c.-152+681T>C		intron_variant	Intron 1 of 1	3		ENSP00000423878.1

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 v4.3

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;