17-43955841-A-G

Position:

• chr17-43955841-A-G

Variant summary

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

The NM_004160.6(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 NM_004160.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.87).
• 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/exons	MANE	Protein	UniProt
PYY	NM_004160.6	c.-126-1866T>C		intron_variant			NP_004151.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000360085.6	c.-126-1866T>C		intron_variant		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

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.963

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.804

Alfa AF: 0.807 Hom.: 6188

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

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: rs231460; hg19: chr17-42033209;