15-84655660-T-C

Position:

• chr15-84655660-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMB	NM_021077.4	c.331-251A>G		intron_variant		ENST00000360476.8	NP_066563.2
NMB	NM_205858.2	c.331-256A>G		intron_variant			NP_995580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000360476.8	c.331-251A>G		intron_variant		1	NM_021077.4	ENSP00000353664	P1
NMB	ENST00000394588.3	c.331-256A>G		intron_variant		1		ENSP00000378089

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

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.839

Alfa AF: 0.849 Hom.: 9291

Bravo AF: 0.865

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs3809508; hg19: chr15-85198891;