4-163345977-C-T

Variant names:

• chr4-163345977-C-T
• rs4632602
• NM_006174.4:c.-81+224C>T

Variant summary

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

The NM_006174.4(NPY5R):​c.-81+224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.85 (52359 hom., cov: 20)
• Consequence: NPY5R NM_006174.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.893 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.-81+224C>T		intron	N/A	NP_006165.1	Q15761
	NPY5R	NM_001317091.2		c.-81+224C>T		intron	N/A	NP_001304020.1	Q15761
	NPY5R	NM_001317092.2		c.-209+224C>T		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.-81+224C>T		intron	N/A	ENSP00000339377.3	Q15761
	NPY5R	ENST00000515560.1	TSL:2	c.-81+224C>T		intron	N/A	ENSP00000423917.1	Q15761
	NPY5R	ENST00000901845.1		c.-84+224C>T		intron	N/A	ENSP00000571904.1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 123448 AN: 145834 Hom.: 52324 Cov.: 20

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.884

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.859

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

GnomAD4 genome AF: 0.847 AC: 123530 AN: 145928 Hom.: 52359 Cov.: 20 AF XY: 0.846 AC XY: 60001 AN XY: 70912

African (AFR) AF: 0.742 AC: 28608 AN: 38536

American (AMR) AF: 0.906 AC: 13092 AN: 14446

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2856 AN: 3438

East Asian (EAS) AF: 0.742 AC: 3595 AN: 4842

South Asian (SAS) AF: 0.846 AC: 3772 AN: 4460

European-Finnish (FIN) AF: 0.891 AC: 8665 AN: 9724

Middle Eastern (MID) AF: 0.882 AC: 254 AN: 288

European-Non Finnish (NFE) AF: 0.894 AC: 60172 AN: 67302

Other (OTH) AF: 0.857 AC: 1711 AN: 1996

Alfa AF: 0.868 Hom.: 11655

Bravo AF: 0.834

Asia WGS AF: 0.817 AC: 2843 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.2
DANN	Benign	0.65
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: rs4632602; hg19: chr4-164267129;