Menu
GeneBe

6-142075893-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002511.4(NMBR):c.928C>T(p.Arg310Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,614,006 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0057 ( 32 hom. )

Consequence

NMBR
NM_002511.4 missense

Scores

3
9
7

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03532988).
BP6
Variant 6-142075893-G-A is Benign according to our data. Variant chr6-142075893-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 770365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NMBRNM_002511.4 linkuse as main transcriptc.928C>T p.Arg310Trp missense_variant 4/4 ENST00000258042.2
NMBRNM_001324307.2 linkuse as main transcriptc.484C>T p.Arg162Trp missense_variant 4/4
NMBRNM_001324308.2 linkuse as main transcriptc.484C>T p.Arg162Trp missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NMBRENST00000258042.2 linkuse as main transcriptc.928C>T p.Arg310Trp missense_variant 4/41 NM_002511.4 P1
NMBRENST00000480652.1 linkuse as main transcriptn.30C>T non_coding_transcript_exon_variant 1/35

Frequencies

GnomAD3 genomes
AF:
0.00444
AC:
675
AN:
152106
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00794
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.000943
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00682
Gnomad OTH
AF:
0.00576
GnomAD3 exomes
AF:
0.00457
AC:
1148
AN:
250936
Hom.:
6
AF XY:
0.00460
AC XY:
624
AN XY:
135596
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00472
Gnomad ASJ exome
AF:
0.00397
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00225
Gnomad FIN exome
AF:
0.00245
Gnomad NFE exome
AF:
0.00680
Gnomad OTH exome
AF:
0.00572
GnomAD4 exome
AF:
0.00568
AC:
8300
AN:
1461782
Hom.:
32
Cov.:
31
AF XY:
0.00565
AC XY:
4105
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.00483
Gnomad4 ASJ exome
AF:
0.00459
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00234
Gnomad4 FIN exome
AF:
0.00292
Gnomad4 NFE exome
AF:
0.00644
Gnomad4 OTH exome
AF:
0.00604
GnomAD4 genome
AF:
0.00443
AC:
675
AN:
152224
Hom.:
5
Cov.:
32
AF XY:
0.00418
AC XY:
311
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.00793
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.000943
Gnomad4 NFE
AF:
0.00682
Gnomad4 OTH
AF:
0.00570
Alfa
AF:
0.00629
Hom.:
8
Bravo
AF:
0.00469
TwinsUK
AF:
0.00674
AC:
25
ALSPAC
AF:
0.00441
AC:
17
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00663
AC:
57
ExAC
AF:
0.00464
AC:
563
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024NMBR: BS2 -
Likely benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.72
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Uncertain
0.11
Cadd
Uncertain
24
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.035
T
MetaSVM
Benign
-0.76
T
MutationAssessor
Pathogenic
3.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-2.3
N
REVEL
Uncertain
0.39
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.029
D
Polyphen
1.0
D
Vest4
0.94
MVP
0.80
MPC
0.31
ClinPred
0.073
T
GERP RS
0.91
Varity_R
0.57
gMVP
0.82

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.

Other links and lift over

dbSNP: rs142626832; hg19: chr6-142397030; API