4-163328333-C-T

Variant summary

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

The NM_000909.6(NPY1R):c.-151-1628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,198 control chromosomes in the GnomAD database, including 52,556 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 0.83 (52556 hom., cov: 32)
• Consequence: NPY1R NM_000909.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY1R	NM_000909.6	c.-151-1628G>A		intron_variant		ENST00000296533.3
NPY1R	XM_005263031.5	c.-151-1628G>A		intron_variant
NPY1R	XM_011532010.4	c.-151-1628G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY1R	ENST00000296533.3	c.-151-1628G>A		intron_variant		1	NM_000909.6	P1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125604 AN: 152080 Hom.: 52548 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.826 AC: 125653 AN: 152198 Hom.: 52556 Cov.: 32 AF XY: 0.827 AC XY: 61575 AN XY: 74416

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.816

Alfa AF: 0.875 Hom.: 80796

Bravo AF: 0.816

Asia WGS AF: 0.831 AC: 2888 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.85
Dann	Benign	0.73

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: rs4691075; hg19: chr4-164249485;