rs9764

Positions:

• chr4-163324253-T-C
• chr4-163324253-T-G

Variant summary

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

The ENST00000296533.3(NPY1R):​c.*1050A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,466 control chromosomes in the GnomAD database, including 7,509 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 0.30 (7458 hom., cov: 32)
  • Exomes 𝑓: 0.43 (51 hom.)
• Consequence: NPY1R ENST00000296533.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY1R	NM_000909.6	c.*1050A>G		3_prime_UTR_variant	3/3	ENST00000296533.3	NP_000900.1
NPY1R	XM_005263031.5	c.*1050A>G		3_prime_UTR_variant	3/3		XP_005263088.1
NPY1R	XM_011532010.4	c.*1050A>G		3_prime_UTR_variant	3/3		XP_011530312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000296533.3	c.*1050A>G		3_prime_UTR_variant	3/3	1	NM_000909.6	ENSP00000354652	P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46194 AN: 151916 Hom.: 7449 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.428 AC: 185 AN: 432 Hom.: 51 Cov.: 0 AF XY: 0.423 AC XY: 110 AN XY: 260

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.304 AC: 46232 AN: 152034 Hom.: 7458 Cov.: 32 AF XY: 0.307 AC XY: 22852 AN XY: 74320

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.274

Alfa AF: 0.270 Hom.: 6221

Bravo AF: 0.296

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.62

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: rs9764; hg19: chr4-164245405; COSMIC: COSV56714201; COSMIC: COSV56714201;