rs12501691

Variant names:

• chr4-163346876-T-A
• rs12501691
• NM_006174.4:c.-80-576T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006174.4. 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
	NPY5R	NM_006174.4	MANE Select	c.-80-576T>A		intron	N/A	NP_006165.1	Q15761
	NPY5R	NM_001317091.2		c.-80-576T>A		intron	N/A	NP_001304020.1	Q15761
	NPY5R	NM_001317092.2		c.-208-361T>A		intron	N/A	NP_001304021.1	Q15761

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY5R	ENST00000338566.8	TSL:1 MANE Select	c.-80-576T>A		intron	N/A	ENSP00000339377.3	Q15761
	NPY5R	ENST00000515560.1	TSL:2	c.-80-576T>A		intron	N/A	ENSP00000423917.1	Q15761
	NPY5R	ENST00000901845.1		c.-83-576T>A		intron	N/A	ENSP00000571904.1

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

African (AFR) AF: 0.0674 AC: 2800 AN: 41562

American (AMR) AF: 0.0960 AC: 1469 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.140 AC: 726 AN: 5182

South Asian (SAS) AF: 0.177 AC: 855 AN: 4826

European-Finnish (FIN) AF: 0.0848 AC: 899 AN: 10604

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0713 AC: 4851 AN: 68006

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.80
PhyloP100		0.89
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: rs12501691; hg19: chr4-164268028;