17-44002197-C-G

Position:

• chr17-44002197-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
PYY	NM_004160.6	c.-463+2194G>C		intron_variant			NP_004151.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000360085.6	c.-463+2194G>C		intron_variant		1		ENSP00000353198	P1

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

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.788

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

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: rs1859223; hg19: chr17-42079565;