4-163335583-A-G

Variant names:

• chr4-163335583-A-G
• rs6837793
• ENST00000511901.1:c.-152+8722T>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+8722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,118 control chromosomes in the GnomAD database, including 55,506 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 0.85 (55506 hom., cov: 31)
• Consequence: NPY1R ENST00000511901.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 8 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 = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY1R	XM_005263031.5	c.-152+8722T>C		intron_variant	Intron 1 of 2		XP_005263088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000511901.1	c.-152+8722T>C		intron_variant	Intron 1 of 1	3		ENSP00000423878.1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129144 AN: 152000 Hom.: 55498 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.849 AC: 129191 AN: 152118 Hom.: 55506 Cov.: 31 AF XY: 0.853 AC XY: 63426 AN XY: 74358

African (AFR) AF: 0.699 AC: 28991 AN: 41460

American (AMR) AF: 0.900 AC: 13759 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3059 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5137 AN: 5174

South Asian (SAS) AF: 0.911 AC: 4398 AN: 4828

European-Finnish (FIN) AF: 0.919 AC: 9735 AN: 10590

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61230 AN: 67994

Other (OTH) AF: 0.843 AC: 1779 AN: 2110

Alfa AF: 0.873 Hom.: 9852

Bravo AF: 0.842

Asia WGS AF: 0.903 AC: 3140 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	4.3
DANN	Benign	0.31
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs6837793; hg19: chr4-164256735;