rs1684664

chr17-43971815-G-Achr17-43971815-G-Cchr17-43971815-G-T

Variant summary

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

The ENST00000360085.6(PYY):c.-462-5283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 151,820 control chromosomes in the GnomAD database, including 52,980 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 0.83 (52980 hom., cov: 29)
• Consequence: PYY ENST00000360085.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

PYY (HGNC:9748): (peptide YY) This gene encodes a member of the neuropeptide Y (NPY) family of peptides. The encoded preproprotein is proteolytically processed to generate two alternative peptide products that differ in length by three amino acids. These peptides, secreted by endocrine cells in the gut, exhibit different binding affinities for each of the neuropeptide Y receptors. Binding of the encoded peptides to these receptors mediates regulation of pancreatic secretion, gut mobility and energy homeostasis. Rare variations in this gene could increase susceptibility to obesity and elevated serum levels of the encoded peptides may be associated with anorexia nervosa. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYY	NM_004160.6	c.-462-5283C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYY	ENST00000360085.6	c.-462-5283C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126256 AN: 151702 Hom.: 52914 Cov.: 29

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.832 AC: 126380 AN: 151820 Hom.: 52980 Cov.: 29 AF XY: 0.841 AC XY: 62378 AN XY: 74210

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.807

Alfa AF: 0.805 Hom.: 5788

Bravo AF: 0.834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.22

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: rs1684664; hg19: chr17-42049183;