4-163331660-T-C

Variant names:

• chr4-163331660-T-C
• rs11100489
• NM_000909.6:c.-152+822A>G

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+822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,158 control chromosomes in the GnomAD database, including 56,379 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 (56379 hom., cov: 32)
• Consequence: NPY1R NM_000909.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 6 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 (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	NM_000909.6	c.-152+822A>G		intron_variant	Intron 1 of 2	ENST00000296533.3	NP_000900.1
NPY1R	XM_011532010.4	c.-1112A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3		XP_011530312.1
NPY1R	XM_011532010.4	c.-1112A>G		5_prime_UTR_variant	Exon 1 of 3		XP_011530312.1
NPY1R	XM_005263031.5	c.-151-4955A>G		intron_variant	Intron 1 of 2		XP_005263088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000296533.3	c.-152+822A>G		intron_variant	Intron 1 of 2	1	NM_000909.6	ENSP00000354652.2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130243 AN: 152040 Hom.: 56373 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.856 AC: 130290 AN: 152158 Hom.: 56379 Cov.: 32 AF XY: 0.860 AC XY: 63922 AN XY: 74364

African (AFR) AF: 0.715 AC: 29647 AN: 41468

American (AMR) AF: 0.902 AC: 13805 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3061 AN: 3468

East Asian (EAS) AF: 0.993 AC: 5131 AN: 5168

South Asian (SAS) AF: 0.912 AC: 4396 AN: 4820

European-Finnish (FIN) AF: 0.918 AC: 9735 AN: 10600

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61610 AN: 68010

Other (OTH) AF: 0.852 AC: 1803 AN: 2116

Alfa AF: 0.868 Hom.: 7456

Bravo AF: 0.850

Asia WGS AF: 0.898 AC: 3124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.5
DANN	Benign	0.60
PhyloP100		0.46
PromoterAI		-0.066	Neutral
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: rs11100489; hg19: chr4-164252812;