rs12507653

Positions:

• chr4-163333181-T-A
• chr4-163333181-T-G

Variant summary

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

The ENST00000511901.1(NPY1R):​c.-151-6476A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,746 control chromosomes in the GnomAD database, including 25,066 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 0.55 (25066 hom., cov: 30)
• Consequence: NPY1R ENST00000511901.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY1R	XM_005263031.5	c.-151-6476A>T		intron_variant			XP_005263088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000511901.1	c.-151-6476A>T		intron_variant		3		ENSP00000423878

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83070 AN: 151628 Hom.: 25070 Cov.: 30

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.547 AC: 83069 AN: 151746 Hom.: 25066 Cov.: 30 AF XY: 0.547 AC XY: 40566 AN XY: 74180

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.564

Alfa AF: 0.471 Hom.: 1430

Bravo AF: 0.547

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12507653; hg19: chr4-164254333;