17-44002197-C-G

Variant names:

• chr17-44002197-C-G
• rs1859223
• ENST00000360085.6:c.-463+2194G>C

Variant summary

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

The ENST00000360085.6(PYY):​c.-463+2194G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,070 control chromosomes in the GnomAD database, including 46,259 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 0.77 (46259 hom., cov: 31)
• Consequence: PYY ENST00000360085.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_004160.6	c.-463+2194G>C		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+2194G>C		intron_variant	Intron 1 of 6	1		ENSP00000353198.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117091 AN: 151952 Hom.: 46225 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.770 AC: 117170 AN: 152070 Hom.: 46259 Cov.: 31 AF XY: 0.763 AC XY: 56692 AN XY: 74344

African (AFR) AF: 0.742 AC: 30768 AN: 41442

American (AMR) AF: 0.661 AC: 10110 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2853 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5146

South Asian (SAS) AF: 0.721 AC: 3474 AN: 4818

European-Finnish (FIN) AF: 0.792 AC: 8398 AN: 10600

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57519 AN: 67982

Other (OTH) AF: 0.788 AC: 1667 AN: 2116

Alfa AF: 0.759 Hom.: 2386

Bravo AF: 0.755

Asia WGS AF: 0.535 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		0.63
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: rs1859223; hg19: chr17-42079565;