NM_002511.4:c.1168C>A

Variant names:

• chr6-142075653-G-T
• rs7453944
• NM_002511.4:c.1168C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002511.4(NMBR):​c.1168C>A​(p.Leu390Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 1,602,362 control chromosomes in the GnomAD database, including 6,698 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.092 (719 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5979 hom.)
• Consequence: NMBR NM_002511.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49
• Publications: 20 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015969574).
• BP6: Variant 6-142075653-G-T is Benign according to our data. Variant chr6-142075653-G-T is described in ClinVar as Benign. ClinVar VariationId is 1252678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

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.1168C>A	p.Leu390Met	missense	Exon 4 of 4	NP_002502.2	P28336
	NMBR	NM_001324307.2		c.724C>A	p.Leu242Met	missense	Exon 4 of 4	NP_001311236.1
	NMBR	NM_001324308.2		c.724C>A	p.Leu242Met	missense	Exon 3 of 3	NP_001311237.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMBR	ENST00000258042.2	TSL:1 MANE Select	c.1168C>A	p.Leu390Met	missense	Exon 4 of 4	ENSP00000258042.1	P28336
	NMBR	ENST00000480652.1	TSL:5	n.179+91C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13944 AN: 152014 Hom.: 714 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0840

GnomAD2 exomes AF: 0.102 AC: 24658 AN: 242382 AF XY: 0.0933

Gnomad AFR exome AF: 0.0998

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.0274

Gnomad EAS exome AF: 0.0912

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0766

Gnomad OTH exome AF: 0.0958

GnomAD4 exome AF: 0.0829 AC: 120231 AN: 1450230 Hom.: 5979 Cov.: 31 AF XY: 0.0801 AC XY: 57721 AN XY: 720260

African (AFR) AF: 0.0961 AC: 3176 AN: 33066

American (AMR) AF: 0.243 AC: 10553 AN: 43344

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 781 AN: 25396

East Asian (EAS) AF: 0.105 AC: 4145 AN: 39466

South Asian (SAS) AF: 0.0526 AC: 4452 AN: 84704

European-Finnish (FIN) AF: 0.107 AC: 5659 AN: 53090

Middle Eastern (MID) AF: 0.0221 AC: 126 AN: 5704

European-Non Finnish (NFE) AF: 0.0782 AC: 86433 AN: 1105558

Other (OTH) AF: 0.0819 AC: 4906 AN: 59902

GnomAD4 genome AF: 0.0918 AC: 13970 AN: 152132 Hom.: 719 Cov.: 32 AF XY: 0.0936 AC XY: 6958 AN XY: 74360

African (AFR) AF: 0.0980 AC: 4065 AN: 41488

American (AMR) AF: 0.160 AC: 2439 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5176

South Asian (SAS) AF: 0.0625 AC: 301 AN: 4816

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10576

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5116 AN: 67998

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0796 Hom.: 2163

Bravo AF: 0.0993

TwinsUK AF: 0.0796 AC: 295

ALSPAC AF: 0.0843 AC: 325

ESP6500AA AF: 0.0969 AC: 427

ESP6500EA AF: 0.0785 AC: 675

ExAC AF: 0.0960 AC: 11653

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.18
Sift	Benign	0.040	D
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.17
MPC		0.30
ClinPred		0.013	T
GERP RS		3.4
Varity_R		0.066
gMVP		0.53
Mutation Taster		=90/10	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: rs7453944; hg19: chr6-142396790; COSMIC: COSV57801092;