chr15-84657523-G-T

Position:

• chr15-84657523-G-T

Variant summary

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

The NM_021077.4(NMB):​c.158-175C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,074 control chromosomes in the GnomAD database, including 29,634 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 0.62 (29634 hom., cov: 33)
• Consequence: NMB NM_021077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMB	NM_021077.4	c.158-175C>A		intron_variant		ENST00000360476.8	NP_066563.2
NMB	XM_017022239.2	c.315C>A	p.Gly105Gly	synonymous_variant	2/2		XP_016877728.1
NMB	NM_205858.2	c.158-175C>A		intron_variant			NP_995580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000360476.8	c.158-175C>A		intron_variant		1	NM_021077.4	ENSP00000353664.3
NMB	ENST00000394588.3	c.158-175C>A		intron_variant		1		ENSP00000378089.3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93861 AN: 151956 Hom.: 29590 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.618 AC: 93951 AN: 152074 Hom.: 29634 Cov.: 33 AF XY: 0.619 AC XY: 46039 AN XY: 74340

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.583

Alfa AF: 0.554 Hom.: 47545

Bravo AF: 0.620

Asia WGS AF: 0.700 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2292462; hg19: chr15-85200754;