chr15-84655131-G-T

Variant names:

• chr15-84655131-G-T
• rs1107179
• ENST00000394588.3:c.*139C>A

Variant summary

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

The ENST00000394588.3(NMB):​c.*139C>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,030,096 control chromosomes in the GnomAD database, including 190,078 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (33916 hom., cov: 32)
  • Exomes 𝑓: 0.59 (156162 hom.)
• Consequence: NMB ENST00000394588.3 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 37 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394588.3. 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.*243C>A		downstream_gene	N/A	NP_066563.2
	NMB	NM_205858.2		c.*139C>A		downstream_gene	N/A	NP_995580.1	P08949-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMB	ENST00000394588.3	TSL:1	c.*139C>A		splice_region	Exon 3 of 3	ENSP00000378089.3	P08949-2
	NMB	ENST00000394588.3	TSL:1	c.*139C>A		3_prime_UTR	Exon 3 of 3	ENSP00000378089.3	P08949-2
	ENSG00000291159	ENST00000762213.1		n.983-4197G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99708 AN: 151920 Hom.: 33859 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.590 AC: 518347 AN: 878058 Hom.: 156162 Cov.: 11 AF XY: 0.587 AC XY: 261890 AN XY: 445874

African (AFR) AF: 0.850 AC: 17503 AN: 20582

American (AMR) AF: 0.712 AC: 18913 AN: 26548

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 9953 AN: 16602

East Asian (EAS) AF: 0.844 AC: 29725 AN: 35200

South Asian (SAS) AF: 0.610 AC: 35685 AN: 58472

European-Finnish (FIN) AF: 0.582 AC: 21077 AN: 36236

Middle Eastern (MID) AF: 0.418 AC: 1811 AN: 4328

European-Non Finnish (NFE) AF: 0.562 AC: 359392 AN: 639954

Other (OTH) AF: 0.605 AC: 24288 AN: 40136

GnomAD4 genome AF: 0.657 AC: 99824 AN: 152038 Hom.: 33916 Cov.: 32 AF XY: 0.658 AC XY: 48923 AN XY: 74298

African (AFR) AF: 0.842 AC: 34934 AN: 41502

American (AMR) AF: 0.667 AC: 10176 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2094 AN: 3468

East Asian (EAS) AF: 0.817 AC: 4224 AN: 5172

South Asian (SAS) AF: 0.619 AC: 2984 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6010 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37609 AN: 67946

Other (OTH) AF: 0.618 AC: 1307 AN: 2114

Alfa AF: 0.583 Hom.: 51255

Bravo AF: 0.670

Asia WGS AF: 0.716 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.41
PhyloP100		0.030
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1107179;

hg19: chr15-85198362;

COSMIC: COSV64685459;

COSMIC: COSV64685459;