rs5577

chr4-163326591-A-C

Variant summary

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

The NM_000909.6(NPY1R):c.-37T>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 0.0228 in 1,292,972 control chromosomes in the GnomAD database, including 589 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 0.022 (102 hom., cov: 33)
  • Exomes 𝑓: 0.023 (487 hom.)
• Consequence: NPY1R NM_000909.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY1R	NM_000909.6	c.-37T>G		5_prime_UTR_variant	2/3	ENST00000296533.3
NPY1R	XM_005263031.5	c.-37T>G		5_prime_UTR_variant	2/3
NPY1R	XM_011532010.4	c.-37T>G		5_prime_UTR_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY1R	ENST00000296533.3	c.-37T>G		5_prime_UTR_variant	2/3	1	NM_000909.6	P1

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3309 AN: 152164 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.00458

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0248

GnomAD3 exomes AF: 0.0285 AC: 5511 AN: 193038 Hom.: 139 AF XY: 0.0291 AC XY: 2978 AN XY: 102194

Gnomad AFR exome AF: 0.00356

Gnomad AMR exome AF: 0.0668

Gnomad ASJ exome AF: 0.0281

Gnomad EAS exome AF: 0.0306

Gnomad SAS exome AF: 0.0630

Gnomad FIN exome AF: 0.00430

Gnomad NFE exome AF: 0.0194

Gnomad OTH exome AF: 0.0335

GnomAD4 exome AF: 0.0230 AC: 26226 AN: 1140690 Hom.: 487 Cov.: 15 AF XY: 0.0241 AC XY: 13879 AN XY: 575218

Gnomad4 AFR exome AF: 0.00386

Gnomad4 AMR exome AF: 0.0633

Gnomad4 ASJ exome AF: 0.0279

Gnomad4 EAS exome AF: 0.0431

Gnomad4 SAS exome AF: 0.0569

Gnomad4 FIN exome AF: 0.00416

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0218 AC: 3314 AN: 152282 Hom.: 102 Cov.: 33 AF XY: 0.0235 AC XY: 1750 AN XY: 74456

Gnomad4 AFR AF: 0.00455

Gnomad4 AMR AF: 0.0749

Gnomad4 ASJ AF: 0.0260

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0184 Hom.: 13

Bravo AF: 0.0234

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	8.1
Dann	Benign	0.50

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: rs5577; hg19: chr4-164247743; COSMIC: COSV56713790;