chr15-84657523-G-T

Variant names:

• chr15-84657523-G-T
• rs2292462
• NM_021077.4:c.158-175C>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.158-175C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,074 control chromosomes in the GnomAD database, including 29,634 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29634 hom., cov: 33)
• Consequence: NMB NM_021077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 29 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:58684):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021077.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMB	NM_021077.4	MANE Select	c.158-175C>A		intron	N/A	NP_066563.2
	NMB	NM_205858.2		c.158-175C>A		intron	N/A	NP_995580.1	P08949-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMB	ENST00000360476.8	TSL:1 MANE Select	c.158-175C>A		intron	N/A	ENSP00000353664.3	P08949-1
	NMB	ENST00000394588.3	TSL:1	c.158-175C>A		intron	N/A	ENSP00000378089.3	P08949-2
	ENSG00000291159	ENST00000762213.1		n.983-1805G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93861 AN: 151956 Hom.: 29590 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 93951 AN: 152074 Hom.: 29634 Cov.: 33 AF XY: 0.619 AC XY: 46039 AN XY: 74340

African (AFR) AF: 0.752 AC: 31175 AN: 41468

American (AMR) AF: 0.547 AC: 8362 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2075 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4171 AN: 5174

South Asian (SAS) AF: 0.617 AC: 2973 AN: 4820

European-Finnish (FIN) AF: 0.569 AC: 6016 AN: 10568

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37466 AN: 67978

Other (OTH) AF: 0.583 AC: 1231 AN: 2112

Alfa AF: 0.568 Hom.: 104418

Bravo AF: 0.620

Asia WGS AF: 0.700 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2292462; hg19: chr15-85200754;