Variant 15-84655375-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_205858.2(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. 12/17 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
NM_205858.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94

Variant links:

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]

NMB links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
NMB	NM_021077.4 linkuse as main transcript	c.365G>A	p.Ter122Ter	stop_retained_variant	3/3	ENST00000360476.8	NP_066563.2	P08949-1
NMB	NM_205858.2 linkuse as main transcript	c.360G>A	p.Met120Ile	missense_variant	3/3		NP_995580.1	P08949-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000394588.3 linkuse as main transcript	c.360G>A	p.Met120Ile	missense_variant	3/3	1		ENSP00000378089.3		P08949-2
NMB	ENST00000360476.8 linkuse as main transcript	c.365G>A	p.Ter122Ter	stop_retained_variant	3/3	1	NM_021077.4	ENSP00000353664.3		P08949-1

Frequencies

GnomAD3 genomes

AF:

0.0655

AC:

9971

AN:

152174

Hom.:

408

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0604

AC XY:

43903

AN XY:

727188

show subpopulations

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.:

AF XY:

0.0643

AC XY:

4789

AN XY:

74482

show subpopulations

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:

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.54

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.30

REVEL

Benign

0.099

Sift

Benign

0.20

Sift4G

Benign

0.088

Polyphen

0.0

Vest4

0.039

MutPred

0.24

Gain of sheet (P = 0.0149);

MPC

0.17

ClinPred

0.0058

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over