4-163351551-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006174.4(NPY5R):​c.1278G>A​(p.Gly426Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,608,182 control chromosomes in the GnomAD database, including 10,686 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 0.10 (815 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9871 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.733 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15345 AN: 151996 Hom.: 812 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.122

GnomAD2 exomes AF: 0.100 AC: 25171 AN: 250892 AF XY: 0.104

Gnomad AFR exome AF: 0.0736

Gnomad AMR exome AF: 0.0586

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.0367

Gnomad FIN exome AF: 0.0982

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.113 AC: 165026 AN: 1456068 Hom.: 9871 Cov.: 30 AF XY: 0.114 AC XY: 82661 AN XY: 724758

African (AFR) AF: 0.0715 AC: 2388 AN: 33386

American (AMR) AF: 0.0623 AC: 2785 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3277 AN: 26112

East Asian (EAS) AF: 0.0595 AC: 2358 AN: 39638

South Asian (SAS) AF: 0.120 AC: 10375 AN: 86120

European-Finnish (FIN) AF: 0.102 AC: 5468 AN: 53386

Middle Eastern (MID) AF: 0.156 AC: 895 AN: 5744

European-Non Finnish (NFE) AF: 0.118 AC: 130475 AN: 1106778

Other (OTH) AF: 0.116 AC: 7005 AN: 60188

GnomAD4 genome AF: 0.101 AC: 15364 AN: 152114 Hom.: 815 Cov.: 32 AF XY: 0.100 AC XY: 7458 AN XY: 74366

African (AFR) AF: 0.0770 AC: 3195 AN: 41512

American (AMR) AF: 0.0830 AC: 1268 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3466

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5180

South Asian (SAS) AF: 0.107 AC: 515 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1068 AN: 10548

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8236 AN: 67984

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.0968 Hom.: 303

Bravo AF: 0.0948

Asia WGS AF: 0.0670 AC: 234 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-0.73
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: rs11946004; hg19: chr4-164272703;