chr4-163342649-A-G

Variant names:

• chr4-163342649-A-G
• rs9996227
• ENST00000511901.1:c.-152+1656T>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+1656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,126 control chromosomes in the GnomAD database, including 56,507 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 0.86 (56507 hom., cov: 31)
• Consequence: NPY1R ENST00000511901.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY1R	XM_005263031.5	c.-152+1656T>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+1656T>C		intron_variant	Intron 1 of 1	3		ENSP00000423878.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130244 AN: 152008 Hom.: 56484 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.857 AC: 130309 AN: 152126 Hom.: 56507 Cov.: 31 AF XY: 0.861 AC XY: 63988 AN XY: 74356

African (AFR) AF: 0.707 AC: 29310 AN: 41450

American (AMR) AF: 0.906 AC: 13850 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3178 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5143 AN: 5176

South Asian (SAS) AF: 0.915 AC: 4413 AN: 4824

European-Finnish (FIN) AF: 0.943 AC: 9994 AN: 10594

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61522 AN: 68000

Other (OTH) AF: 0.853 AC: 1805 AN: 2116

Alfa AF: 0.851 Hom.: 9086

Bravo AF: 0.847

Asia WGS AF: 0.911 AC: 3169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		-0.0010

Splicing

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

Other links and lift over

dbSNP: rs9996227; hg19: chr4-164263801;