4-163328333-C-T

Variant names:

• chr4-163328333-C-T
• rs4691075
• NM_000909.6:c.-151-1628G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000909.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY1R	NM_000909.6	MANE Select	c.-151-1628G>A		intron	N/A	NP_000900.1	P25929

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY1R	ENST00000296533.3	TSL:1 MANE Select	c.-151-1628G>A		intron	N/A	ENSP00000354652.2	P25929
	NPY1R	ENST00000916226.1		c.-1779G>A		5_prime_UTR	Exon 1 of 2	ENSP00000586285.1
	NPY1R	ENST00000875543.1		c.-151-1628G>A		intron	N/A	ENSP00000545602.1

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

African (AFR) AF: 0.687 AC: 28475 AN: 41472

American (AMR) AF: 0.821 AC: 12543 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2970 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4981 AN: 5184

South Asian (SAS) AF: 0.854 AC: 4119 AN: 4824

European-Finnish (FIN) AF: 0.914 AC: 9703 AN: 10614

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60125 AN: 68028

Other (OTH) AF: 0.816 AC: 1727 AN: 2116

Alfa AF: 0.868 Hom.: 99655

Bravo AF: 0.816

Asia WGS AF: 0.831 AC: 2888 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
DANN	Benign	0.73
PhyloP100		-0.30
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: rs4691075; hg19: chr4-164249485;