15-84657289-G-T

Variant names:

• chr15-84657289-G-T
• rs1051168
• NM_021077.4:c.217C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021077.4(NMB):​c.217C>A​(p.Pro73Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,597,686 control chromosomes in the GnomAD database, including 49,271 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3530 hom., cov: 31)
  • Exomes 𝑓: 0.25 (45741 hom.)
• Consequence: NMB NM_021077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• Publications: 57 publications found

Genes affected

NMB (HGNC:7842): (neuromedin B) This gene encodes a member of the bombesin-like family of neuropeptides, which negatively regulate eating behavior. The encoded protein may regulate colonic smooth muscle contraction through binding to its cognate receptor, the neuromedin B receptor (NMBR). Polymorphisms of this gene may be associated with hunger, weight gain and obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ENSG00000291159 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003712654).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMB	NM_021077.4	c.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 3	ENST00000360476.8	NP_066563.2
NMB	NM_205858.2	c.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 3		NP_995580.1
NMB	XM_017022239.2	c.*111C>A		downstream_gene_variant			XP_016877728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000360476.8	c.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 3	1	NM_021077.4	ENSP00000353664.3
NMB	ENST00000394588.3	c.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 3	1		ENSP00000378089.3
ENSG00000291159	ENST00000762213.1	n.983-2039G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29100 AN: 152038 Hom.: 3531 Cov.: 31

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.220 AC: 48830 AN: 222298 AF XY: 0.226

Gnomad AFR exome AF: 0.0423

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.246 AC: 355260 AN: 1445528 Hom.: 45741 Cov.: 33 AF XY: 0.246 AC XY: 176840 AN XY: 717900

African (AFR) AF: 0.0389 AC: 1288 AN: 33132

American (AMR) AF: 0.178 AC: 7538 AN: 42380

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6409 AN: 25698

East Asian (EAS) AF: 0.110 AC: 4263 AN: 38922

South Asian (SAS) AF: 0.199 AC: 16619 AN: 83642

European-Finnish (FIN) AF: 0.220 AC: 11539 AN: 52548

Middle Eastern (MID) AF: 0.376 AC: 2154 AN: 5734

European-Non Finnish (NFE) AF: 0.264 AC: 291696 AN: 1103788

Other (OTH) AF: 0.230 AC: 13754 AN: 59684

GnomAD4 genome AF: 0.191 AC: 29095 AN: 152158 Hom.: 3530 Cov.: 31 AF XY: 0.188 AC XY: 14007 AN XY: 74378

African (AFR) AF: 0.0471 AC: 1958 AN: 41542

American (AMR) AF: 0.197 AC: 3008 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3470

East Asian (EAS) AF: 0.126 AC: 651 AN: 5172

South Asian (SAS) AF: 0.183 AC: 884 AN: 4826

European-Finnish (FIN) AF: 0.224 AC: 2363 AN: 10572

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18389 AN: 67970

Other (OTH) AF: 0.207 AC: 437 AN: 2108

Alfa AF: 0.248 Hom.: 16653

Bravo AF: 0.185

TwinsUK AF: 0.264 AC: 980

ALSPAC AF: 0.252 AC: 972

ESP6500AA AF: 0.0518 AC: 228

ESP6500EA AF: 0.266 AC: 2288

ExAC AF: 0.208 AC: 25237

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.063	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PhyloP100		0.41
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.079
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.10
ClinPred		0.015	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.097
gMVP		0.13
Mutation Taster		=99/1	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: rs1051168; hg19: chr15-85200520; COSMIC: COSV64685521; COSMIC: COSV64685521;