4-163329645-A-G

Variant names:

• chr4-163329645-A-G
• rs7687423
• NM_000909.6:c.-152+2837T>C

Variant summary

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

The NM_000909.6(NPY1R):​c.-152+2837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,612 control chromosomes in the GnomAD database, including 22,119 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 0.53 (22119 hom., cov: 30)
• Consequence: NPY1R NM_000909.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 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.-152+2837T>C		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.-152+2837T>C		intron	N/A	ENSP00000354652.2	P25929
	NPY1R	ENST00000916226.1		c.-3091T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000586285.1
	NPY1R	ENST00000916226.1		c.-3091T>C		5_prime_UTR	Exon 1 of 2	ENSP00000586285.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80171 AN: 151500 Hom.: 22123 Cov.: 30

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.529 AC: 80183 AN: 151612 Hom.: 22119 Cov.: 30 AF XY: 0.526 AC XY: 38979 AN XY: 74058

African (AFR) AF: 0.380 AC: 15696 AN: 41324

American (AMR) AF: 0.592 AC: 9020 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3466

East Asian (EAS) AF: 0.398 AC: 2046 AN: 5146

South Asian (SAS) AF: 0.583 AC: 2803 AN: 4812

European-Finnish (FIN) AF: 0.479 AC: 4992 AN: 10416

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41570 AN: 67886

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.594 Hom.: 34864

Bravo AF: 0.530

Asia WGS AF: 0.478 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.078
DANN	Benign	0.70
PhyloP100		-0.23
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: rs7687423; hg19: chr4-164250797;