rs11100493

Variant names:

• chr4-163345607-T-C
• rs11100493
• NM_006174.4:c.-120-107T>C

Variant summary

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

The NM_006174.4(NPY5R):​c.-120-107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,266 control chromosomes in the GnomAD database, including 554 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 0.080 (554 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NPY5R NM_006174.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY5R	NM_006174.4	c.-120-107T>C		intron_variant	Intron 1 of 3	ENST00000338566.8	NP_006165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY5R	ENST00000338566.8	c.-120-107T>C		intron_variant	Intron 1 of 3	1	NM_006174.4	ENSP00000339377.3
NPY5R	ENST00000515560.1	c.-121+104T>C		intron_variant	Intron 1 of 3	2		ENSP00000423917.1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12123 AN: 152148 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0774

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0796 AC: 12115 AN: 152266 Hom.: 554 Cov.: 32 AF XY: 0.0817 AC XY: 6084 AN XY: 74446

African (AFR) AF: 0.0674 AC: 2801 AN: 41542

American (AMR) AF: 0.0966 AC: 1478 AN: 15302

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

East Asian (EAS) AF: 0.142 AC: 735 AN: 5188

South Asian (SAS) AF: 0.184 AC: 891 AN: 4832

European-Finnish (FIN) AF: 0.0849 AC: 900 AN: 10596

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0717 AC: 4876 AN: 68014

Other (OTH) AF: 0.0766 AC: 162 AN: 2116

Alfa AF: 0.0743 Hom.: 153

Bravo AF: 0.0815

Asia WGS AF: 0.152 AC: 526 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		-0.80
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: rs11100493; hg19: chr4-164266759;