ENST00000360085.6:c.-126-1866T>C

Variant names:

• chr17-43955841-A-G
• rs231460
• ENST00000360085.6:c.-126-1866T>C

Variant summary

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

The ENST00000360085.6(PYY):​c.-126-1866T>C 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 52,938 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 (52938 hom., cov: 29)
• Consequence: PYY ENST00000360085.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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 rank	MANE	Protein	UniProt
PYY	NM_004160.6	c.-126-1866T>C		intron_variant	Intron 3 of 6		NP_004151.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000360085.6	c.-126-1866T>C		intron_variant	Intron 3 of 6	1		ENSP00000353198.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126183 AN: 151702 Hom.: 52871 Cov.: 29

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.832 AC: 126308 AN: 151820 Hom.: 52938 Cov.: 29 AF XY: 0.840 AC XY: 62288 AN XY: 74164

African (AFR) AF: 0.900 AC: 37241 AN: 41372

American (AMR) AF: 0.854 AC: 13029 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2823 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5137 AN: 5142

South Asian (SAS) AF: 0.963 AC: 4637 AN: 4814

European-Finnish (FIN) AF: 0.838 AC: 8845 AN: 10554

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 51978 AN: 67900

Other (OTH) AF: 0.804 AC: 1695 AN: 2108

Alfa AF: 0.810 Hom.: 6497

Bravo AF: 0.834

Asia WGS AF: 0.973 AC: 3385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.76
PhyloP100		0.034
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: rs231460; hg19: chr17-42033209;