Genetic Variant MANBA:c.2416-10delT (chr4-102632290-GA-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005908.4(MANBA):c.2416-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 23011 hom., cov: 0)

Exomes 𝑓: 0.52 ( 140227 hom. )

Consequence

MANBA
NM_005908.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.178

Publications

3 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics

MANBA links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005908.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 4-102632290-GA-G is Benign according to our data. Variant chr4-102632290-GA-G is described in ClinVar as Benign. ClinVar VariationId is 403070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005908.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	NM_005908.4	MANE Select	c.2416-10delT		intron	N/A	NP_005899.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MANBA	ENST00000647097.2	MANE Select	c.2416-10delT	intron	N/A	ENSP00000495247.1	O00462
MANBA	ENST00000642252.1		c.2554-10delT	intron	N/A	ENSP00000495483.1	A0A2R8YEC9
MANBA	ENST00000954426.1		c.2515-10delT	intron	N/A	ENSP00000624485.1

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

82581

AN:

148198

Hom.:

22977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.565

GnomAD2 exomes

AF:

0.598

AC:

122664

AN:

205224

AF XY:

0.590

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.736

Gnomad ASJ exome

AF:

0.560

Gnomad EAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.555

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.521

AC:

630786

AN:

1210052

Hom.:

140227

Cov.:

AF XY:

0.521

AC XY:

315924

AN XY:

606580

show subpopulations

African (AFR)

AF:

0.616

AC:

17277

AN:

28030

American (AMR)

AF:

0.714

AC:

29276

AN:

40992

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

11696

AN:

22392

East Asian (EAS)

AF:

0.533

AC:

18179

AN:

34128

South Asian (SAS)

AF:

0.495

AC:

36601

AN:

73982

European-Finnish (FIN)

AF:

0.517

AC:

24048

AN:

46504

Middle Eastern (MID)

AF:

0.579

AC:

2962

AN:

5120

European-Non Finnish (NFE)

AF:

0.510

AC:

463532

AN:

908294

Other (OTH)

AF:

0.538

AC:

27215

AN:

50610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

17811

35622

53432

71243

89054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13636

27272

40908

54544

68180

<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:

0.557

AC:

82661

AN:

148304

Hom.:

23011

Cov.:

AF XY:

0.557

AC XY:

40212

AN XY:

72224

show subpopulations

African (AFR)

AF:

0.634

AC:

25783

AN:

40672

American (AMR)

AF:

0.621

AC:

9310

AN:

15002

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1761

AN:

3416

East Asian (EAS)

AF:

0.525

AC:

2637

AN:

5026

South Asian (SAS)

AF:

0.461

AC:

2149

AN:

4660

European-Finnish (FIN)

AF:

0.496

AC:

4812

AN:

9708

Middle Eastern (MID)

AF:

0.614

AC:

178

AN:

290

European-Non Finnish (NFE)

AF:

0.516

AC:

34365

AN:

66588

Other (OTH)

AF:

0.560

AC:

1145

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1820

3640

5459

7279

9099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.434

Hom.:

1436

Bravo

AF:

0.561

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Beta-D-mannosidosis (3)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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4-102632290-GAA-GA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over