rs9895585

Variant names:

• chr17-43987619-A-C
• rs9895585
• ENST00000360085.6:c.-463+16772T>G

Variant summary

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

The ENST00000360085.6(PYY):​c.-463+16772T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,956 control chromosomes in the GnomAD database, including 2,000 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 0.12 (2000 hom., cov: 32)
• Consequence: PYY ENST00000360085.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_004160.6	c.-463+16772T>G		intron_variant	Intron 1 of 6		NP_004151.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000360085.6	c.-463+16772T>G		intron_variant	Intron 1 of 6	1		ENSP00000353198.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18034 AN: 151838 Hom.: 1993 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.119 AC: 18070 AN: 151956 Hom.: 2000 Cov.: 32 AF XY: 0.116 AC XY: 8627 AN XY: 74280

African (AFR) AF: 0.289 AC: 11987 AN: 41428

American (AMR) AF: 0.0729 AC: 1113 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3464

East Asian (EAS) AF: 0.134 AC: 695 AN: 5172

South Asian (SAS) AF: 0.0699 AC: 336 AN: 4804

European-Finnish (FIN) AF: 0.0197 AC: 208 AN: 10568

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3207 AN: 67950

Other (OTH) AF: 0.102 AC: 215 AN: 2100

Alfa AF: 0.123 Hom.: 1066

Bravo AF: 0.132

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.58
PhyloP100		-1.5
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: rs9895585; hg19: chr17-42064987;