15-84655131-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394588.3(NMB):c.*139C>A variant causes a 3 prime UTR 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. 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 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMB	NM_021077.4			downstream_gene_variant		ENST00000360476.8
NMB	NM_205858.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMB	ENST00000394588.3	c.*139C>A		3_prime_UTR_variant	3/3	1
NMB	ENST00000360476.8			downstream_gene_variant		1	NM_021077.4	P1

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

Gnomad4 AFR exome AF: 0.850

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.605

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

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.618

Alfa AF: 0.569 Hom.: 35713

Bravo AF: 0.670

Asia WGS AF: 0.716 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.6
Dann	Benign	0.41

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: rs1107179; hg19: chr15-85198362; COSMIC: COSV64685459; COSMIC: COSV64685459;