17-43988557-A-G

Position:

• chr17-43988557-A-G

Variant summary

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

The ENST00000360085.6(PYY):​c.-463+15834T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,880 control chromosomes in the GnomAD database, including 22,548 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 0.53 (22548 hom., cov: 30)
• Consequence: PYY ENST00000360085.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYY	NM_004160.6	c.-463+15834T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYY	ENST00000360085.6	c.-463+15834T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80875 AN: 151762 Hom.: 22549 Cov.: 30

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.532 AC: 80874 AN: 151880 Hom.: 22548 Cov.: 30 AF XY: 0.527 AC XY: 39121 AN XY: 74244

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.585

Alfa AF: 0.608 Hom.: 45268

Bravo AF: 0.523

Asia WGS AF: 0.446 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.55

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: rs1618809; hg19: chr17-42065925;