chr15-84655131-G-C

Variant names:

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

Variant summary

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

The ENST00000394588.3(NMB):​c.*139C>G variant causes a splice region 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. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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:):

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 (BayesDel_noAF=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMB	NM_021077.4	MANE Select	c.*243C>G		downstream_gene	N/A	NP_066563.2
	NMB	NM_205858.2		c.*139C>G		downstream_gene	N/A	NP_995580.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 880346 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 447042

African (AFR) AF: 0.00 AC: 0 AN: 20604

American (AMR) AF: 0.00 AC: 0 AN: 26600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16646

East Asian (EAS) AF: 0.00 AC: 0 AN: 35238

South Asian (SAS) AF: 0.00 AC: 0 AN: 58636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 641730

Other (OTH) AF: 0.00 AC: 0 AN: 40244

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		0.030

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: rs1107179; hg19: chr15-85198362;