4-163324511-A-G

Position:

• chr4-163324511-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000909.6(NPY1R):​c.*792T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,064 control chromosomes in the GnomAD database, including 55,404 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 (55403 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: NPY1R NM_000909.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• 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/exons	MANE	Protein	UniProt
NPY1R	NM_000909.6	c.*792T>C		3_prime_UTR_variant	3/3	ENST00000296533.3	NP_000900.1
NPY1R	XM_005263031.5	c.*792T>C		3_prime_UTR_variant	3/3		XP_005263088.1
NPY1R	XM_011532010.4	c.*792T>C		3_prime_UTR_variant	3/3		XP_011530312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000296533.3	c.*792T>C		3_prime_UTR_variant	3/3	1	NM_000909.6	ENSP00000354652	P1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128850 AN: 151942 Hom.: 55397 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.852

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.750

GnomAD4 genome AF: 0.848 AC: 128904 AN: 152060 Hom.: 55403 Cov.: 31 AF XY: 0.852 AC XY: 63281 AN XY: 74308

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.844

Alfa AF: 0.876 Hom.: 17981

Bravo AF: 0.840

Asia WGS AF: 0.892 AC: 3099 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs4552421; hg19: chr4-164245663;