rs17598561

chr15-84655375-C-T

Variant summary

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

The ENST00000394588.3(NMB):c.360G>A(p.Met120Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,614,058 control chromosomes in the GnomAD database, including 3,373 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.066 (409 hom., cov: 33)
  • Exomes 𝑓: 0.061 (2964 hom.)
• Consequence: NMB ENST00000394588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

Genes affected

NMB (HGNC:7842): (neuromedin B) This gene encodes a member of the bombesin-like family of neuropeptides, which negatively regulate eating behavior. The encoded protein may regulate colonic smooth muscle contraction through binding to its cognate receptor, the neuromedin B receptor (NMBR). Polymorphisms of this gene may be associated with hunger, weight gain and obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028395653).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMB	NM_021077.4	c.365G>A	p.Ter122=	stop_retained_variant	3/3	ENST00000360476.8
NMB	NM_205858.2	c.360G>A	p.Met120Ile	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMB	ENST00000394588.3	c.360G>A	p.Met120Ile	missense_variant	3/3	1
NMB	ENST00000360476.8	c.365G>A	p.Ter122=	stop_retained_variant	3/3	1	NM_021077.4	P1

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9971 AN: 152174 Hom.: 408 Cov.: 33

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0635

GnomAD3 exomes AF: 0.0532 AC: 13363 AN: 251274 Hom.: 444 AF XY: 0.0531 AC XY: 7216 AN XY: 135840

Gnomad AFR exome AF: 0.0883

Gnomad AMR exome AF: 0.0330

Gnomad ASJ exome AF: 0.0918

Gnomad EAS exome AF: 0.00277

Gnomad SAS exome AF: 0.0520

Gnomad FIN exome AF: 0.0537

Gnomad NFE exome AF: 0.0592

Gnomad OTH exome AF: 0.0538

GnomAD4 exome AF: 0.0607 AC: 88722 AN: 1461766 Hom.: 2964 Cov.: 31 AF XY: 0.0604 AC XY: 43903 AN XY: 727188

Gnomad4 AFR exome AF: 0.0920

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.0879

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.0551

Gnomad4 FIN exome AF: 0.0516

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.0616

GnomAD4 genome AF: 0.0655 AC: 9979 AN: 152292 Hom.: 409 Cov.: 33 AF XY: 0.0643 AC XY: 4789 AN XY: 74482

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0616

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0612 Hom.: 682

Bravo AF: 0.0648

TwinsUK AF: 0.0674 AC: 250

ALSPAC AF: 0.0690 AC: 266

ESP6500AA AF: 0.0897 AC: 395

ESP6500EA AF: 0.0658 AC: 566

ExAC AF: 0.0529 AC: 6429

Asia WGS AF: 0.0270 AC: 96 AN: 3478

EpiCase AF: 0.0598

EpiControl AF: 0.0595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	13
Dann	Benign	0.54
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.099
Sift	Benign	0.20	T
Sift4G	Benign	0.088	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.24		Gain of sheet (P = 0.0149);
MPC		0.17
ClinPred		0.0058	T
GERP RS		2.7
gMVP		0.057

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: rs17598561; hg19: chr15-85198606; COSMIC: COSV64685483; COSMIC: COSV64685483;