rs1051168

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021077.4(NMB):​c.217C>T​(p.Pro73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NMB NM_021077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040698707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMB	NM_021077.4	c.217C>T	p.Pro73Ser	missense_variant	Exon 2 of 3	ENST00000360476.8	NP_066563.2
NMB	NM_205858.2	c.217C>T	p.Pro73Ser	missense_variant	Exon 2 of 3		NP_995580.1
NMB	XM_017022239.2	c.*111C>T		downstream_gene_variant			XP_016877728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000360476.8	c.217C>T	p.Pro73Ser	missense_variant	Exon 2 of 3	1	NM_021077.4	ENSP00000353664.3
NMB	ENST00000394588.3	c.217C>T	p.Pro73Ser	missense_variant	Exon 2 of 3	1		ENSP00000378089.3
ENSG00000291159	ENST00000762213.1	n.983-2039G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446048 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 718160

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 42436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25710

East Asian (EAS) AF: 0.00 AC: 0 AN: 38944

South Asian (SAS) AF: 0.00 AC: 0 AN: 83688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104132

Other (OTH) AF: 0.00 AC: 0 AN: 59702

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.78
DEOGEN2	Benign	0.062	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		0.41
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.050
Sift	Benign	0.67	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.0060	B;B
Vest4		0.058
MutPred		0.14		Gain of phosphorylation at P73 (P = 0.0426);Gain of phosphorylation at P73 (P = 0.0426);
MVP		0.22
MPC		0.18
ClinPred		0.057	T
GERP RS		-1.4
Varity_R		0.062
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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;