4-163342649-A-G

Variant names:

• chr4-163342649-A-G
• rs9996227
• ENST00000967840.1:c.-152+2125T>C

Variant summary

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

The ENST00000511901.1(NPY1R):​c.-152+1656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,126 control chromosomes in the GnomAD database, including 56,507 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 0.86 (56507 hom., cov: 31)
• Consequence: NPY1R ENST00000511901.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511901.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY1R	ENST00000967840.1		c.-152+2125T>C		intron	N/A	ENSP00000637899.1
	NPY1R	ENST00000511901.1	TSL:3	c.-152+1656T>C		intron	N/A	ENSP00000423878.1	D6RC44

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130244 AN: 152008 Hom.: 56484 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.857 AC: 130309 AN: 152126 Hom.: 56507 Cov.: 31 AF XY: 0.861 AC XY: 63988 AN XY: 74356

African (AFR) AF: 0.707 AC: 29310 AN: 41450

American (AMR) AF: 0.906 AC: 13850 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3178 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5143 AN: 5176

South Asian (SAS) AF: 0.915 AC: 4413 AN: 4824

European-Finnish (FIN) AF: 0.943 AC: 9994 AN: 10594

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61522 AN: 68000

Other (OTH) AF: 0.853 AC: 1805 AN: 2116

Alfa AF: 0.851 Hom.: 9086

Bravo AF: 0.847

Asia WGS AF: 0.911 AC: 3169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		-0.0010

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9996227;

hg19: chr4-164263801;