4-163351551-G-T

Variant names:

• chr4-163351551-G-T
• rs11946004
• NM_006174.4:c.1278G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006174.4(NPY5R):​c.1278G>T​(p.Gly426Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NPY5R NM_006174.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• Publications: 11 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.733 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY5R	NM_006174.4	c.1278G>T	p.Gly426Gly	synonymous_variant	Exon 4 of 4	ENST00000338566.8	NP_006165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY5R	ENST00000338566.8	c.1278G>T	p.Gly426Gly	synonymous_variant	Exon 4 of 4	1	NM_006174.4	ENSP00000339377.3
NPY5R	ENST00000506953.1	c.1278G>T	p.Gly426Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000423474.1
NPY5R	ENST00000515560.1	c.1278G>T	p.Gly426Gly	synonymous_variant	Exon 4 of 4	2		ENSP00000423917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250892 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456818 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725088

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1107452

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.57
DANN	Benign	0.52
PhyloP100		-0.73

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: rs11946004; hg19: chr4-164272703;