rs17598561

Variant names:

• chr15-84655375-C-T
• rs17598561
• ENST00000394588.3:c.360G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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
• Publications: 22 publications found

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]

ENSG00000291159 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NMB	NM_021077.4	c.365G>A	p.Ter122Ter	stop_retained_variant	Exon 3 of 3	ENST00000360476.8	NP_066563.2
NMB	NM_205858.2	c.360G>A	p.Met120Ile	missense_variant	Exon 3 of 3		NP_995580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000394588.3	c.360G>A	p.Met120Ile	missense_variant	Exon 3 of 3	1		ENSP00000378089.3
NMB	ENST00000360476.8	c.365G>A	p.Ter122Ter	stop_retained_variant	Exon 3 of 3	1	NM_021077.4	ENSP00000353664.3
ENSG00000291159	ENST00000762213.1	n.983-3953C>T		intron_variant	Intron 3 of 3

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

GnomAD2 exomes AF: 0.0532 AC: 13363 AN: 251274 AF XY: 0.0531

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 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

African (AFR) AF: 0.0920 AC: 3081 AN: 33476

American (AMR) AF: 0.0347 AC: 1553 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 2295 AN: 26122

East Asian (EAS) AF: 0.00106 AC: 42 AN: 39700

South Asian (SAS) AF: 0.0551 AC: 4753 AN: 86256

European-Finnish (FIN) AF: 0.0516 AC: 2754 AN: 53414

Middle Eastern (MID) AF: 0.0512 AC: 295 AN: 5764

European-Non Finnish (NFE) AF: 0.0632 AC: 70230 AN: 1111926

Other (OTH) AF: 0.0616 AC: 3719 AN: 60392

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

African (AFR) AF: 0.0917 AC: 3812 AN: 41554

American (AMR) AF: 0.0431 AC: 660 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5180

South Asian (SAS) AF: 0.0536 AC: 259 AN: 4828

European-Finnish (FIN) AF: 0.0515 AC: 547 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0616 AC: 4189 AN: 68030

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0618 Hom.: 976

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
AlphaMissense	Benign	0.17
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
PhyloP100		2.9
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
Mutation Taster		=95/5	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: rs17598561; hg19: chr15-85198606; COSMIC: COSV64685483; COSMIC: COSV64685483;