rs33977775

chr8-52940311-A-T

Variant summary

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

The NM_005285.5(NPBWR1):c.404A>T(p.Tyr135Phe) variant causes a missense change. The variant allele was found at a frequency of 0.115 in 1,612,328 control chromosomes in the GnomAD database, including 11,480 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.095 (838 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10642 hom.)
• Consequence: NPBWR1 NM_005285.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.09

Genes affected

NPBWR1 (HGNC:4522): (neuropeptides B and W receptor 1) Predicted to enable G protein-coupled receptor activity and neuropeptide binding activity. Involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in neuron projection. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035134554).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPBWR1	NM_005285.5	c.404A>T	p.Tyr135Phe	missense_variant	2/2	ENST00000674939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPBWR1	ENST00000674939.1	c.404A>T	p.Tyr135Phe	missense_variant	2/2		NM_005285.5	P1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14490 AN: 152076 Hom.: 839 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.117

GnomAD3 exomes AF: 0.114 AC: 28213 AN: 247484 Hom.: 1752 AF XY: 0.117 AC XY: 15745 AN XY: 134698

Gnomad AFR exome AF: 0.0256

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.117 AC: 171474 AN: 1460134 Hom.: 10642 Cov.: 32 AF XY: 0.118 AC XY: 85559 AN XY: 726494

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0952 AC: 14493 AN: 152194 Hom.: 838 Cov.: 33 AF XY: 0.0968 AC XY: 7199 AN XY: 74408

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.120

Alfa AF: 0.120 Hom.: 860

Bravo AF: 0.0918

TwinsUK AF: 0.116 AC: 431

ALSPAC AF: 0.122 AC: 471

ESP6500AA AF: 0.0298 AC: 131

ESP6500EA AF: 0.118 AC: 1016

ExAC AF: 0.112 AC: 13544

Asia WGS AF: 0.107 AC: 369 AN: 3478

EpiCase AF: 0.128

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.11
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.00031	P
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.20
MPC		1.1
ClinPred		0.018	T
GERP RS		5.1
Varity_R		0.74
gMVP		0.51

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: rs33977775; hg19: chr8-53852871; COSMIC: COSV58696536;