rs12501691

Positions:

• chr4-163346876-T-A

Variant summary

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

The NM_006174.4(NPY5R):​c.-80-576T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,268 control chromosomes in the GnomAD database, including 535 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 0.079 (535 hom., cov: 33)
• Consequence: NPY5R NM_006174.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY5R	NM_006174.4	c.-80-576T>A		intron_variant		ENST00000338566.8	NP_006165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY5R	ENST00000338566.8	c.-80-576T>A		intron_variant		1	NM_006174.4	ENSP00000339377	P1
NPY5R	ENST00000515560.1	c.-80-576T>A		intron_variant		2		ENSP00000423917	P1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12041 AN: 152150 Hom.: 539 Cov.: 33

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0776

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

GnomAD4 genome AF: 0.0790 AC: 12034 AN: 152268 Hom.: 535 Cov.: 33 AF XY: 0.0812 AC XY: 6045 AN XY: 74456

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0960

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0848

Gnomad4 NFE AF: 0.0713

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0764 Hom.: 62

Bravo AF: 0.0812

Asia WGS AF: 0.149 AC: 516 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.80

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: rs12501691; hg19: chr4-164268028;