rs5577

Variant names:

• chr4-163326591-A-C
• rs5577
• NM_000909.6:c.-37T>G

Variant summary

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

The NM_000909.6(NPY1R):​c.-37T>G variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 8 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=-0.91).
• 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 rank	MANE	Protein	UniProt
NPY1R	NM_000909.6	c.-37T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 3	ENST00000296533.3	NP_000900.1
NPY1R	NM_000909.6	c.-37T>G		5_prime_UTR_variant	Exon 2 of 3	ENST00000296533.3	NP_000900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000296533.3	c.-37T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 3	1	NM_000909.6	ENSP00000354652.2
NPY1R	ENST00000296533.3	c.-37T>G		5_prime_UTR_variant	Exon 2 of 3	1	NM_000909.6	ENSP00000354652.2

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

GnomAD2 exomes AF: 0.0285 AC: 5511 AN: 193038 AF XY: 0.0291

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 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

African (AFR) AF: 0.00386 AC: 101 AN: 26180

American (AMR) AF: 0.0633 AC: 2239 AN: 35382

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 565 AN: 20218

East Asian (EAS) AF: 0.0431 AC: 1640 AN: 38084

South Asian (SAS) AF: 0.0569 AC: 3882 AN: 68236

European-Finnish (FIN) AF: 0.00416 AC: 208 AN: 50042

Middle Eastern (MID) AF: 0.0200 AC: 98 AN: 4902

European-Non Finnish (NFE) AF: 0.0192 AC: 16285 AN: 848432

Other (OTH) AF: 0.0245 AC: 1208 AN: 49214

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

African (AFR) AF: 0.00455 AC: 189 AN: 41570

American (AMR) AF: 0.0749 AC: 1144 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 90 AN: 3468

East Asian (EAS) AF: 0.0328 AC: 170 AN: 5188

South Asian (SAS) AF: 0.0587 AC: 283 AN: 4822

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0185 AC: 1255 AN: 68010

Other (OTH) AF: 0.0274 AC: 58 AN: 2116

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
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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