rs11724320

Positions:

• chr4-163346771-T-C

Variant summary

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

The NM_006174.4(NPY5R):​c.-80-681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,030 control chromosomes in the GnomAD database, including 25,087 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 0.56 (25087 hom., cov: 32)
• Consequence: NPY5R NM_006174.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY5R	NM_006174.4	c.-80-681T>C		intron_variant		ENST00000338566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY5R	ENST00000338566.8	c.-80-681T>C		intron_variant		1	NM_006174.4	P1
NPY5R	ENST00000515560.1	c.-80-681T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85210 AN: 151912 Hom.: 25077 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.561 AC: 85255 AN: 152030 Hom.: 25087 Cov.: 32 AF XY: 0.556 AC XY: 41332 AN XY: 74306

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.556

Alfa AF: 0.602 Hom.: 4215

Bravo AF: 0.556

Asia WGS AF: 0.380 AC: 1319 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.49

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: rs11724320; hg19: chr4-164267923;