rs11946004

Positions:

• chr4-163351551-G-A
• chr4-163351551-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006174.4(NPY5R):​c.1278G>A​(p.Gly426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,608,182 control chromosomes in the GnomAD database, including 10,686 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 0.10 (815 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9871 hom.)
• Consequence: NPY5R NM_006174.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733

Genes affected

NPY5R (HGNC:7958): (neuropeptide Y receptor Y5) The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.733 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY5R	NM_006174.4	c.1278G>A	p.Gly426=	synonymous_variant	4/4	ENST00000338566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY5R	ENST00000338566.8	c.1278G>A	p.Gly426=	synonymous_variant	4/4	1	NM_006174.4	P1
NPY5R	ENST00000506953.1	c.1278G>A	p.Gly426=	synonymous_variant	1/1			P1
NPY5R	ENST00000515560.1	c.1278G>A	p.Gly426=	synonymous_variant	4/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15345 AN: 151996 Hom.: 812 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.100 AC: 25171 AN: 250892 Hom.: 1422 AF XY: 0.104 AC XY: 14167 AN XY: 135710

Gnomad AFR exome AF: 0.0736

Gnomad AMR exome AF: 0.0586

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.0367

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.0982

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.113 AC: 165026 AN: 1456068 Hom.: 9871 Cov.: 30 AF XY: 0.114 AC XY: 82661 AN XY: 724758

Gnomad4 AFR exome AF: 0.0715

Gnomad4 AMR exome AF: 0.0623

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0595

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.101 AC: 15364 AN: 152114 Hom.: 815 Cov.: 32 AF XY: 0.100 AC XY: 7458 AN XY: 74366

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0968 Hom.: 303

Bravo AF: 0.0948

Asia WGS AF: 0.0670 AC: 234 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.65
DANN	Benign	0.51

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: rs11946004; hg19: chr4-164272703;