8-52940311-A-T

Variant names:

• chr8-52940311-A-T
• rs33977775
• NM_005285.5:c.404A>T

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005285.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPBWR1	NM_005285.5	MANE Select	c.404A>T	p.Tyr135Phe	missense	Exon 2 of 2	NP_005276.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPBWR1	ENST00000674939.1	MANE Select	c.404A>T	p.Tyr135Phe	missense	Exon 2 of 2	ENSP00000501711.1

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

GnomAD2 exomes AF: 0.114 AC: 28213 AN: 247484 AF XY: 0.117

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 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

African (AFR) AF: 0.0240 AC: 803 AN: 33470

American (AMR) AF: 0.105 AC: 4682 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3157 AN: 26126

East Asian (EAS) AF: 0.130 AC: 5169 AN: 39686

South Asian (SAS) AF: 0.117 AC: 10049 AN: 86256

European-Finnish (FIN) AF: 0.114 AC: 5917 AN: 51904

Middle Eastern (MID) AF: 0.0853 AC: 492 AN: 5768

European-Non Finnish (NFE) AF: 0.121 AC: 134509 AN: 1111848

Other (OTH) AF: 0.111 AC: 6696 AN: 60372

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

African (AFR) AF: 0.0260 AC: 1082 AN: 41554

American (AMR) AF: 0.108 AC: 1647 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.130 AC: 670 AN: 5136

South Asian (SAS) AF: 0.118 AC: 571 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8296 AN: 67986

Other (OTH) AF: 0.120 AC: 254 AN: 2114

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 v4.9

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
PhyloP100		7.1
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
Mutation Taster		=90/10	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: rs33977775; hg19: chr8-53852871; COSMIC: COSV58696536;