rs4958531

Positions:

• chr5-152392277-T-C

Variant summary

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

The NM_020167.5(NMUR2):​c.1162A>G​(p.Met388Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,544 control chromosomes in the GnomAD database, including 28,634 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (2080 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26554 hom.)
• Consequence: NMUR2 NM_020167.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

Genes affected

NMUR2 (HGNC:16454): (neuromedin U receptor 2) This gene encodes a protein from the G-protein coupled receptor 1 family. This protein is a receptor for neuromedin U, which is a neuropeptide that is widely distributed in the gut and central nervous system. This receptor plays an important role in the regulation of food intake and body weight. [provided by RefSeq, Jul 2008]

ENSG00000286749 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015337467).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMUR2	NM_020167.5	c.1162A>G	p.Met388Val	missense_variant	4/4	ENST00000255262.4	NP_064552.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMUR2	ENST00000255262.4	c.1162A>G	p.Met388Val	missense_variant	4/4	1	NM_020167.5	ENSP00000255262.4
ENSG00000286749	ENST00000663460.1	n.216+17064T>C		intron_variant
ENSG00000286749	ENST00000663819.1	n.183+17064T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22034 AN: 151998 Hom.: 2083 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.184 AC: 46119 AN: 251328 Hom.: 5361 AF XY: 0.182 AC XY: 24713 AN XY: 135830

Gnomad AFR exome AF: 0.0417

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.0318

Gnomad SAS exome AF: 0.190

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.183 AC: 268060 AN: 1461428 Hom.: 26554 Cov.: 35 AF XY: 0.183 AC XY: 133079 AN XY: 727014

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0232

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.145 AC: 22023 AN: 152116 Hom.: 2080 Cov.: 32 AF XY: 0.145 AC XY: 10820 AN XY: 74368

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.142

Alfa AF: 0.174 Hom.: 5262

Bravo AF: 0.147

TwinsUK AF: 0.204 AC: 757

ALSPAC AF: 0.193 AC: 743

ESP6500AA AF: 0.0533 AC: 235

ESP6500EA AF: 0.181 AC: 1556

ExAC AF: 0.174 AC: 21190

Asia WGS AF: 0.0850 AC: 297 AN: 3478

EpiCase AF: 0.187

EpiControl AF: 0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0010
DANN	Benign	0.20
DEOGEN2	Benign	0.014	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.3	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.047
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.15
ClinPred		0.00071	T
GERP RS		-7.2
Varity_R		0.034
gMVP		0.31

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: rs4958531; hg19: chr5-151771838; COSMIC: COSV54919843; COSMIC: COSV54919843;