6-142088531-C-T

Variant names:

• chr6-142088531-C-T
• rs372711016
• NM_002511.4:c.128G>A
• NMBR p.Arg43His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002511.4(NMBR):​c.128G>A​(p.Arg43His) variant causes a missense change. The variant allele was found at a frequency of 0.000242 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: NMBR NM_002511.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07
• Publications: 5 publications found

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-AS1 (HGNC:40406): (NMBR antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002511.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMBR	NM_002511.4	MANE Select	c.128G>A	p.Arg43His	missense	Exon 2 of 4	NP_002502.2	P28336
	NMBR	NM_001324307.2		c.-22-9628G>A		intron	N/A	NP_001311236.1
	NMBR	NM_001324308.2		c.-22-9628G>A		intron	N/A	NP_001311237.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMBR	ENST00000258042.2	TSL:1 MANE Select	c.128G>A	p.Arg43His	missense	Exon 2 of 4	ENSP00000258042.1	P28336
	NMBR-AS1	ENST00000454401.1	TSL:5	n.142+157C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152062 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000295 AC: 74 AN: 250958 AF XY: 0.000346

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000247 AC: 361 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.000275 AC XY: 200 AN XY: 727230

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00116 AC: 100 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1111994

Other (OTH) AF: 0.000248 AC: 15 AN: 60394

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152180 Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10 AN XY: 74402

African (AFR) AF: 0.000144 AC: 6 AN: 41526

American (AMR) AF: 0.000196 AC: 3 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000311 Hom.: 0

Bravo AF: 0.000208

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.23
Sift	Benign	0.15	T
Sift4G	Benign	0.44	T
Varity_R		0.089
gMVP		0.74
Mutation Taster		=42/58	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs372711016;

hg19: chr6-142409668;

COSMIC: COSV57801294;