15-84655660-T-G

Variant names:

• chr15-84655660-T-G
• rs3809508
• NM_021077.4:c.331-251A>C

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.331-251A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NMB NM_021077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 13 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMB	NM_021077.4	c.331-251A>C		intron_variant	Intron 2 of 2	ENST00000360476.8	NP_066563.2
NMB	NM_205858.2	c.331-256A>C		intron_variant	Intron 2 of 2		NP_995580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000360476.8	c.331-251A>C		intron_variant	Intron 2 of 2	1	NM_021077.4	ENSP00000353664.3
NMB	ENST00000394588.3	c.331-256A>C		intron_variant	Intron 2 of 2	1		ENSP00000378089.3
ENSG00000291159	ENST00000762213.1	n.983-3668T>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.50
PhyloP100		0.96

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: rs3809508; hg19: chr15-85198891;