chr9-137086979-C-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The ENST00000542372(MAN1B1):c.-21C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,572,138 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
MAN1B1
ENST00000542372 5_prime_UTR
ENST00000542372 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.661
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]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BS1
Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000244 (347/1419744) while in subpopulation MID AF = 0.0043 (23/5346). AF 95% confidence interval is 0.00294. There are 1 homozygotes in GnomAdExome4. There are 182 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000328 AC: 50AN: 152276Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
50
AN:
152276
Hom.:
Cov.:
34
Gnomad AFR
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GnomAD2 exomes AF: 0.000268 AC: 49AN: 182732 AF XY: 0.000285 show subpopulations
GnomAD2 exomes
AF:
AC:
49
AN:
182732
AF XY:
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GnomAD4 exome AF: 0.000244 AC: 347AN: 1419744Hom.: 1 Cov.: 30 AF XY: 0.000259 AC XY: 182AN XY: 702630 show subpopulations
GnomAD4 exome
AF:
AC:
347
AN:
1419744
Hom.:
Cov.:
30
AF XY:
AC XY:
182
AN XY:
702630
Gnomad4 AFR exome
AF:
AC:
17
AN:
32938
Gnomad4 AMR exome
AF:
AC:
25
AN:
37840
Gnomad4 ASJ exome
AF:
AC:
2
AN:
25256
Gnomad4 EAS exome
AF:
AC:
0
AN:
38152
Gnomad4 SAS exome
AF:
AC:
3
AN:
81008
Gnomad4 FIN exome
AF:
AC:
2
AN:
48506
Gnomad4 NFE exome
AF:
AC:
232
AN:
1091800
Gnomad4 Remaining exome
AF:
AC:
43
AN:
58898
Heterozygous variant carriers
0
19
38
58
77
96
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
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Age
GnomAD4 genome AF: 0.000328 AC: 50AN: 152394Hom.: 0 Cov.: 34 AF XY: 0.000349 AC XY: 26AN XY: 74532 show subpopulations
GnomAD4 genome
AF:
AC:
50
AN:
152394
Hom.:
Cov.:
34
AF XY:
AC XY:
26
AN XY:
74532
Gnomad4 AFR
AF:
AC:
0.000480839
AN:
0.000480839
Gnomad4 AMR
AF:
AC:
0.000587851
AN:
0.000587851
Gnomad4 ASJ
AF:
AC:
0.000288184
AN:
0.000288184
Gnomad4 EAS
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AC:
0
AN:
0
Gnomad4 SAS
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AC:
0
AN:
0
Gnomad4 FIN
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0
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0
Gnomad4 NFE
AF:
AC:
0.000220439
AN:
0.000220439
Gnomad4 OTH
AF:
AC:
0.00189036
AN:
0.00189036
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
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0.95
Allele balance
Genome Het
Variant carriers
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Age
Alfa
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Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual Disability, Recessive Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Mutation Taster
=300/0
polymorphism
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at