4-163347762-C-T

Variant names:

• chr4-163347762-C-T
• rs7678265
• NM_006174.4:c.-10+240C>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.-10+240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,178 control chromosomes in the GnomAD database, including 382 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 0.064 (382 hom., cov: 32)
• Consequence: NPY5R NM_006174.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY5R	NM_006174.4	c.-10+240C>T		intron_variant	Intron 3 of 3	ENST00000338566.8	NP_006165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY5R	ENST00000338566.8	c.-10+240C>T		intron_variant	Intron 3 of 3	1	NM_006174.4	ENSP00000339377.3
NPY5R	ENST00000515560.1	c.-10+240C>T		intron_variant	Intron 3 of 3	2		ENSP00000423917.1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9699 AN: 152060 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0819

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

GnomAD4 genome AF: 0.0637 AC: 9697 AN: 152178 Hom.: 382 Cov.: 32 AF XY: 0.0620 AC XY: 4616 AN XY: 74406

African (AFR) AF: 0.0205 AC: 853 AN: 41526

American (AMR) AF: 0.0575 AC: 878 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3472

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5190

South Asian (SAS) AF: 0.0430 AC: 207 AN: 4816

European-Finnish (FIN) AF: 0.0723 AC: 766 AN: 10588

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0937 AC: 6371 AN: 67988

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0457 Hom.: 107

Bravo AF: 0.0604

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7678265; hg19: chr4-164268914; COSMIC: COSV58451331; COSMIC: COSV58451331;