4-163347762-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	UniProt
NPY5R	NM_006174.4	c.-10+240C>T		intron_variant		ENST00000338566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY5R	ENST00000338566.8	c.-10+240C>T		intron_variant		1	NM_006174.4	P1
NPY5R	ENST00000515560.1	c.-10+240C>T		intron_variant		2		P1

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

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0430

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.0937

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0401 Hom.: 47

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7678265; hg19: chr4-164268914; COSMIC: COSV58451331; COSMIC: COSV58451331;