Genetic Variant NMB:c.*139C>A (chr15-84655131-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000394588.3(NMB):c.*139C>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,030,096 control chromosomes in the GnomAD database, including 190,078 homozygotes. 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: 𝑓 0.66 ( 33916 hom., cov: 32)

Exomes 𝑓: 0.59 ( 156162 hom. )

Consequence

NMB
ENST00000394588.3 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

37 publications found

Variant links:

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]

NMB links:

ENSG00000291159 (HGNC:):

ENSG00000291159 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMB	NM_021077.4 link	c.*243C>A		downstream_gene_variant		ENST00000360476.8	NP_066563.2
NMB	NM_205858.2 link	c.*139C>A		downstream_gene_variant			NP_995580.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NMB	ENST00000394588.3 link	c.*139C>A	splice_region_variant	Exon 3 of 3	1		ENSP00000378089.3
NMB	ENST00000394588.3 link	c.*139C>A	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000378089.3
ENSG00000291159	ENST00000762213.1 link	n.983-4197G>T	intron_variant	Intron 3 of 3
NMB	ENST00000360476.8 link	c.*243C>A	downstream_gene_variant		1	NM_021077.4	ENSP00000353664.3

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99708

AN:

151920

Hom.:

33859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.842

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.604

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.620

GnomAD4 exome

AF:

0.590

AC:

518347

AN:

878058

Hom.:

156162

Cov.:

AF XY:

0.587

AC XY:

261890

AN XY:

445874

show subpopulations

African (AFR)

AF:

0.850

AC:

17503

AN:

20582

American (AMR)

AF:

0.712

AC:

18913

AN:

26548

Ashkenazi Jewish (ASJ)

AF:

0.600

AC:

9953

AN:

16602

East Asian (EAS)

AF:

0.844

AC:

29725

AN:

35200

South Asian (SAS)

AF:

0.610

AC:

35685

AN:

58472

European-Finnish (FIN)

AF:

0.582

AC:

21077

AN:

36236

Middle Eastern (MID)

AF:

0.418

AC:

1811

AN:

4328

European-Non Finnish (NFE)

AF:

0.562

AC:

359392

AN:

639954

Other (OTH)

AF:

0.605

AC:

24288

AN:

40136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9737

19475

29212

38950

48687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8562

17124

25686

34248

42810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.657

AC:

99824

AN:

152038

Hom.:

33916

Cov.:

AF XY:

0.658

AC XY:

48923

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.842

AC:

34934

AN:

41502

American (AMR)

AF:

0.667

AC:

10176

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

2094

AN:

3468

East Asian (EAS)

AF:

0.817

AC:

4224

AN:

5172

South Asian (SAS)

AF:

0.619

AC:

2984

AN:

4820

European-Finnish (FIN)

AF:

0.570

AC:

6010

AN:

10550

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.554

AC:

37609

AN:

67946

Other (OTH)

AF:

0.618

AC:

1307

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1683

3367

5050

6734

8417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.583

Hom.:

51255

Bravo

AF:

0.670

Asia WGS

AF:

0.716

AC:

2489

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.6

(source)

DANN

Benign

0.41

PhyloP100

0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over