NM_021077.4:c.331-251A>G

Variant names:

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

Variant summary

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

The NM_021077.4(NMB):​c.331-251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,160 control chromosomes in the GnomAD database, including 56,020 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 0.86 (56020 hom., 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:58684):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMB	NM_021077.4	MANE Select	c.331-251A>G		intron	N/A	NP_066563.2
	NMB	NM_205858.2		c.331-256A>G		intron	N/A	NP_995580.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMB	ENST00000360476.8	TSL:1 MANE Select	c.331-251A>G		intron	N/A	ENSP00000353664.3
	NMB	ENST00000394588.3	TSL:1	c.331-256A>G		intron	N/A	ENSP00000378089.3
	ENSG00000291159	ENST00000762213.1		n.983-3668T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130347 AN: 152042 Hom.: 55959 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.857 AC: 130464 AN: 152160 Hom.: 56020 Cov.: 31 AF XY: 0.856 AC XY: 63672 AN XY: 74374

African (AFR) AF: 0.904 AC: 37539 AN: 41514

American (AMR) AF: 0.874 AC: 13365 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3000 AN: 3470

East Asian (EAS) AF: 0.944 AC: 4877 AN: 5164

South Asian (SAS) AF: 0.804 AC: 3879 AN: 4824

European-Finnish (FIN) AF: 0.796 AC: 8419 AN: 10576

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56597 AN: 68004

Other (OTH) AF: 0.839 AC: 1773 AN: 2114

Alfa AF: 0.851 Hom.: 9603

Bravo AF: 0.865

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		0.96
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

Other links and lift over

dbSNP: rs3809508; hg19: chr15-85198891;