chr17-43988557-A-G

Variant names:

• chr17-43988557-A-G
• rs1618809
• ENST00000360085.6:c.-463+15834T>C

Variant summary

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

The NM_004160.6(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 NM_004160.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004160.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYY	NM_004160.6		c.-463+15834T>C		intron	N/A	NP_004151.4	P10082-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYY	ENST00000360085.6	TSL:1	c.-463+15834T>C		intron	N/A	ENSP00000353198.1	P10082-1
	PYY	ENST00000917562.1		c.-463+15834T>C		intron	N/A	ENSP00000587621.1

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

African (AFR) AF: 0.401 AC: 16601 AN: 41414

American (AMR) AF: 0.486 AC: 7417 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2302 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1258 AN: 5154

South Asian (SAS) AF: 0.583 AC: 2800 AN: 4806

European-Finnish (FIN) AF: 0.538 AC: 5677 AN: 10546

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42864 AN: 67936

Other (OTH) AF: 0.585 AC: 1228 AN: 2098

Alfa AF: 0.599 Hom.: 101628

Bravo AF: 0.523

Asia WGS AF: 0.446 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.55
PhyloP100		1.1
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: rs1618809; hg19: chr17-42065925;