rs118117962

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BS1BS2

The NM_016219.5(MAN1B1):c.2052C>T(p.Tyr684Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,800 control chromosomes in the GnomAD database, including 1,258 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 95 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1163 hom. )

Consequence

MAN1B1
NM_016219.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.75

Publications

5 publications found

Variant links:

Genes affected

MAN1B1 (HGNC:6823): (mannosidase alpha class 1B member 1) This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1,2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause autosomal-recessive intellectual disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Dec 2011]

MAN1B1 Gene-Disease associations (from GenCC):

MAN1B1-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Rafiq syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MAN1B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 9-137108543-C-T is Benign according to our data. Variant chr9-137108543-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.75 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0289 (4397/152298) while in subpopulation NFE AF = 0.0418 (2845/68020). AF 95% confidence interval is 0.0405. There are 95 homozygotes in GnomAd4. There are 2092 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 95 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MAN1B1	NM_016219.5 link	c.2052C>T	p.Tyr684Tyr	synonymous_variant	Exon 13 of 13	ENST00000371589.9	NP_057303.2
MAN1B1	NR_045720.2 link	n.2042C>T		non_coding_transcript_exon_variant	Exon 13 of 13
MAN1B1	NR_045721.2 link	n.2198C>T		non_coding_transcript_exon_variant	Exon 14 of 14
MAN1B1	XM_006716945.5 link	c.*581C>T		downstream_gene_variant			XP_006717008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1B1	ENST00000371589.9 link	c.2052C>T	p.Tyr684Tyr	synonymous_variant	Exon 13 of 13	1	NM_016219.5	ENSP00000360645.4

Frequencies

GnomAD3 genomes

AF:

0.0289

AC:

4397

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00719

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0714

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0302

AC:

7598

AN:

251480

AF XY:

0.0311

show subpopulations

Gnomad AFR exome

AF:

0.00566

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.0687

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0263

Gnomad NFE exome

AF:

0.0418

Gnomad OTH exome

AF:

0.0366

GnomAD4 exome

AF:

0.0373

AC:

54570

AN:

1461502

Hom.:

1163

Cov.:

AF XY:

0.0370

AC XY:

26920

AN XY:

727054

show subpopulations

African (AFR)

AF:

0.00535

AC:

179

AN:

33478

American (AMR)

AF:

0.0186

AC:

833

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0687

AC:

1796

AN:

26132

East Asian (EAS)

AF:

0.000151

AC:

AN:

39698

South Asian (SAS)

AF:

0.0214

AC:

1849

AN:

86258

European-Finnish (FIN)

AF:

0.0279

AC:

1481

AN:

53168

Middle Eastern (MID)

AF:

0.0418

AC:

241

AN:

5768

European-Non Finnish (NFE)

AF:

0.0415

AC:

46122

AN:

1111888

Other (OTH)

AF:

0.0342

AC:

2063

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3182

6364

9546

12728

15910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1678

3356

5034

6712

8390

<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:

0.0289

AC:

4397

AN:

152298

Hom.:

Cov.:

AF XY:

0.0281

AC XY:

2092

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00717

AC:

298

AN:

41572

American (AMR)

AF:

0.0299

AC:

457

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0714

AC:

248

AN:

3472

East Asian (EAS)

AF:

0.00231

AC:

AN:

5186

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4822

European-Finnish (FIN)

AF:

0.0288

AC:

306

AN:

10612

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0418

AC:

2845

AN:

68020

Other (OTH)

AF:

0.0298

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

217

435

652

870

1087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0381

Hom.:

Bravo

AF:

0.0285

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rafiq syndrome

Benign:2

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 14, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Inborn genetic diseases

Benign:1

Apr 20, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.65

(source)

DANN

Benign

0.82

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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