rs1051168

Positions:

• chr15-84657289-G-C
• chr15-84657289-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021077.4(NMB):​c.217C>G​(p.Pro73Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P73T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NMB NM_021077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072307736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMB	NM_021077.4	c.217C>G	p.Pro73Ala	missense_variant	2/3	ENST00000360476.8	NP_066563.2
NMB	NM_205858.2	c.217C>G	p.Pro73Ala	missense_variant	2/3		NP_995580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000360476.8	c.217C>G	p.Pro73Ala	missense_variant	2/3	1	NM_021077.4	ENSP00000353664.3
NMB	ENST00000394588.3	c.217C>G	p.Pro73Ala	missense_variant	2/3	1		ENSP00000378089.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000450 AC: 1 AN: 222298 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 120524

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.033
Sift	Benign	0.26	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.088	B;B
Vest4		0.23
MutPred		0.15		Loss of glycosylation at P73 (P = 0.0441);Loss of glycosylation at P73 (P = 0.0441);
MVP		0.28
MPC		0.30
ClinPred		0.13	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.076

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: rs1051168; hg19: chr15-85200520;