6-142075653-G-T

Position:

• chr6-142075653-G-T

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMBR	NM_002511.4	c.1168C>A	p.Leu390Met	missense_variant	4/4	ENST00000258042.2	NP_002502.2
NMBR	NM_001324307.2	c.724C>A	p.Leu242Met	missense_variant	4/4		NP_001311236.1
NMBR	NM_001324308.2	c.724C>A	p.Leu242Met	missense_variant	3/3		NP_001311237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMBR	ENST00000258042.2	c.1168C>A	p.Leu390Met	missense_variant	4/4	1	NM_002511.4	ENSP00000258042	P1
NMBR	ENST00000480652.1	n.179+91C>A		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.102 AC: 24658 AN: 242382 Hom.: 1833 AF XY: 0.0933 AC XY: 12210 AN XY: 130920

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 SAS exome AF: 0.0515

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

Gnomad4 AFR exome AF: 0.0961

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.0308

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0526

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0782

Gnomad4 OTH exome AF: 0.0819

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

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0753 Hom.: 1016

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 29, 2020

This variant is associated with the following publications: (PMID: 31724192) -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.54	P
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

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

Other links and lift over

dbSNP: rs7453944; hg19: chr6-142396790; COSMIC: COSV57801092;