6-142075893-G-A

Position:

• chr6-142075893-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.00

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 -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 GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMBR	NM_002511.4	c.928C>T	p.Arg310Trp	missense_variant	4/4	ENST00000258042.2	NP_002502.2
NMBR	NM_001324307.2	c.484C>T	p.Arg162Trp	missense_variant	4/4		NP_001311236.1
NMBR	NM_001324308.2	c.484C>T	p.Arg162Trp	missense_variant	3/3		NP_001311237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMBR	ENST00000258042.2	c.928C>T	p.Arg310Trp	missense_variant	4/4	1	NM_002511.4	ENSP00000258042	P1
NMBR	ENST00000480652.1	n.30C>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 675 AN: 152106 Hom.: 5 Cov.: 32

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

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

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

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	NMBR: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Other links and lift over

dbSNP: rs142626832; hg19: chr6-142397030;