rs2272697

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005908.4(MANBA):c.2368T>C(p.Leu790Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,613,786 control chromosomes in the GnomAD database, including 224,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23406 hom., cov: 32)

Exomes 𝑓: 0.52 ( 201098 hom. )

Consequence

MANBA
NM_005908.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.00

Publications

38 publications found

Variant links:

Genes affected

MANBA (HGNC:6831): (mannosidase beta) This gene encodes a member of the glycosyl hydrolase 2 family. The encoded protein localizes to the lysosome where it is the final exoglycosidase in the pathway for N-linked glycoprotein oligosaccharide catabolism. Mutations in this gene are associated with beta-mannosidosis, a lysosomal storage disease that has a wide spectrum of neurological involvement. [provided by RefSeq, Jul 2008]

MANBA Gene-Disease associations (from GenCC):

beta-mannosidosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

MANBA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 4-102634835-A-G is Benign according to our data. Variant chr4-102634835-A-G is described in ClinVar as [Benign]. Clinvar id is 95320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANBA	NM_005908.4 link	c.2368T>C	p.Leu790Leu	synonymous_variant	Exon 16 of 17	ENST00000647097.2	NP_005899.3	O00462
MANBA	XM_047415692.1 link	c.2293T>C	p.Leu765Leu	synonymous_variant	Exon 17 of 18		XP_047271648.1
MANBA	XM_047415693.1 link	c.2293T>C	p.Leu765Leu	synonymous_variant	Exon 17 of 18		XP_047271649.1
MANBA	XM_047415694.1 link	c.1720T>C	p.Leu574Leu	synonymous_variant	Exon 12 of 13		XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2 link	c.2368T>C	p.Leu790Leu	synonymous_variant	Exon 16 of 17		NM_005908.4	ENSP00000495247.1		O00462

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83484

AN:

151954

Hom.:

23368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.556

GnomAD2 exomes

AF:

0.541

AC:

135905

AN:

251324

AF XY:

0.529

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.487

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.533

GnomAD4 exome

AF:

0.521

AC:

762192

AN:

1461714

Hom.:

201098

Cov.:

AF XY:

0.518

AC XY:

376758

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.634

AC:

21229

AN:

33478

American (AMR)

AF:

0.724

AC:

32388

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12879

AN:

26136

East Asian (EAS)

AF:

0.493

AC:

19585

AN:

39700

South Asian (SAS)

AF:

0.461

AC:

39744

AN:

86252

European-Finnish (FIN)

AF:

0.476

AC:

25435

AN:

53418

Middle Eastern (MID)

AF:

0.569

AC:

3266

AN:

5736

European-Non Finnish (NFE)

AF:

0.518

AC:

575514

AN:

1111886

Other (OTH)

AF:

0.532

AC:

32152

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

22448

44896

67344

89792

112240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16766

33532

50298

67064

83830

<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:

0.550

AC:

83569

AN:

152072

Hom.:

23406

Cov.:

AF XY:

0.548

AC XY:

40779

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.631

AC:

26160

AN:

41488

American (AMR)

AF:

0.618

AC:

9450

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1762

AN:

3468

East Asian (EAS)

AF:

0.517

AC:

2669

AN:

5160

South Asian (SAS)

AF:

0.451

AC:

2176

AN:

4828

European-Finnish (FIN)

AF:

0.471

AC:

4987

AN:

10580

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34506

AN:

67944

Other (OTH)

AF:

0.549

AC:

1157

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1942

3883

5825

7766

9708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.529

Hom.:

33809

Bravo

AF:

0.567

Asia WGS

AF:

0.505

AC:

1753

AN:

3478

EpiCase

AF:

0.516

EpiControl

AF:

0.504

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Mar 21, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 16, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Beta-D-mannosidosis

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.6

(source)

DANN

Benign

0.50

PhyloP100

3.0

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over