chr17-43953041-G-A

Variant names:

• chr17-43953041-G-A
• rs162430
• ENST00000592796.2:c.*64C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394028.1(PYY):​c.270-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,590,194 control chromosomes in the GnomAD database, including 29,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6392 hom., cov: 32)
  • Exomes 𝑓: 0.14 (23419 hom.)
• Consequence: PYY NM_001394028.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0700
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-43953041-G-A is Benign according to our data. Variant chr17-43953041-G-A is described in ClinVar as [Benign]. Clinvar id is 1243115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1	c.270-61C>T		intron_variant	Intron 3 of 3	ENST00000692052.1	NP_001380957.1
PYY	NM_001394029.1	c.*64C>T		3_prime_UTR_variant	Exon 3 of 3		NP_001380958.1
PYY	NM_004160.6	c.270-61C>T		intron_variant	Intron 6 of 6		NP_004151.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000592796.2	c.*64C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000467310.1
PYY	ENST00000692052.1	c.270-61C>T		intron_variant	Intron 3 of 3		NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.270-61C>T		intron_variant	Intron 6 of 6	1		ENSP00000353198.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35699 AN: 152060 Hom.: 6348 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.135 AC: 194429 AN: 1438016 Hom.: 23419 Cov.: 31 AF XY: 0.137 AC XY: 97538 AN XY: 713794

African (AFR) AF: 0.456 AC: 14691 AN: 32204

American (AMR) AF: 0.296 AC: 11779 AN: 39826

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4142 AN: 24740

East Asian (EAS) AF: 0.680 AC: 26803 AN: 39418

South Asian (SAS) AF: 0.216 AC: 18082 AN: 83630

European-Finnish (FIN) AF: 0.138 AC: 7265 AN: 52792

Middle Eastern (MID) AF: 0.166 AC: 934 AN: 5638

European-Non Finnish (NFE) AF: 0.0915 AC: 100698 AN: 1100508

Other (OTH) AF: 0.169 AC: 10035 AN: 59260

GnomAD4 genome AF: 0.235 AC: 35804 AN: 152178 Hom.: 6392 Cov.: 32 AF XY: 0.240 AC XY: 17840 AN XY: 74394

African (AFR) AF: 0.436 AC: 18100 AN: 41524

American (AMR) AF: 0.257 AC: 3924 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3444 AN: 5130

South Asian (SAS) AF: 0.232 AC: 1121 AN: 4832

European-Finnish (FIN) AF: 0.137 AC: 1454 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0954 AC: 6488 AN: 68000

Other (OTH) AF: 0.220 AC: 465 AN: 2110

Alfa AF: 0.149 Hom.: 2791

Bravo AF: 0.257

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 14551916) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.8
DANN	Benign	0.92
PhyloP100		0.070
Mutation Taster		=99/1	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: rs162430; hg19: chr17-42030409; COSMIC: COSV63970071;