Variant 6-142078827-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002511.4(NMBR):c.499A>G(p.Ile167Val) variant causes a missense change. The variant allele was found at a frequency of 0.00307 in 1,613,874 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 17 hom. )

Consequence

NMBR
NM_002511.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.96

Variant links:

Genes affected

NMBR (HGNC:7843): (neuromedin B receptor) This gene encodes a 7-transmembrane G protein-coupled receptor that binds neuromedin B, which is a growth factor and mitogen for gastrointestinal epithelial tissue and for normal and neoplastic lung. This receptor may play a role in smooth muscle contraction, neuronal responses, and the regulation of cell growth. Antagonists of this receptor have a potential therapeutic use in inhibiting tumor cell growth. Polymorphisms in this gene may be associated with a susceptibility for schizophrenia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

NMBR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04389009).

BP6

Variant 6-142078827-T-C is Benign according to our data. Variant chr6-142078827-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656945.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NMBR	NM_002511.4 linkuse as main transcript	c.499A>G	p.Ile167Val	missense_variant	3/4	ENST00000258042.2	NP_002502.2
NMBR	NM_001324307.2 linkuse as main transcript	c.55A>G	p.Ile19Val	missense_variant	3/4		NP_001311236.1
NMBR	NM_001324308.2 linkuse as main transcript	c.55A>G	p.Ile19Val	missense_variant	2/3		NP_001311237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMBR	ENST00000258042.2 linkuse as main transcript	c.499A>G	p.Ile167Val	missense_variant	3/4	1	NM_002511.4	ENSP00000258042	P1

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

324

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000823

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000662

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00168

AC:

419

AN:

249286

Hom.:

AF XY:

0.00151

AC XY:

204

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00317

AC:

4633

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

2231

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000917

Gnomad4 NFE exome

AF:

0.00391

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.00213

AC:

324

AN:

151998

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.000821

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000662

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00160

AC:

194

EpiCase

AF:

0.00327

EpiControl

AF:

0.00284

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

NMBR: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.51

M_CAP

Benign

0.019

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.64

REVEL

Uncertain

0.33

Sift

Benign

0.23

Sift4G

Benign

0.21

Polyphen

0.97

Vest4

0.56

MVP

0.75

MPC

0.20

ClinPred

0.057

GERP RS

4.3

Varity_R

0.11

gMVP

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over