Variant chr9-137088416-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016219.5(MAN1B1):c.328+233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,564,906 control chromosomes in the GnomAD database, including 128,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14147 hom., cov: 33)

Exomes 𝑓: 0.40 ( 114192 hom. )

Consequence

MAN1B1
NM_016219.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.514

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 links:

MAN1B1 (HGNC:):

MAN1B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 9-137088416-C-T is Benign according to our data. Variant chr9-137088416-C-T is described in ClinVar as [Benign]. Clinvar id is 1229424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAN1B1	NM_016219.5 linkuse as main transcript	c.328+233C>T	intron_variant	ENST00000371589.9	NP_057303.2	Q9UKM7
MAN1B1	XM_006716945.5 linkuse as main transcript	c.328+233C>T	intron_variant		XP_006717008.1	H0YG20
MAN1B1	NR_045720.2 linkuse as main transcript	n.343+233C>T	intron_variant
MAN1B1	NR_045721.2 linkuse as main transcript	n.474+18C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1B1	ENST00000371589.9 linkuse as main transcript	c.328+233C>T		intron_variant		1	NM_016219.5	ENSP00000360645.4		Q9UKM7

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64795

AN:

152014

Hom.:

14130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.439

GnomAD3 exomes

AF:

0.439

AC:

101544

AN:

231338

Hom.:

23192

AF XY:

0.434

AC XY:

55423

AN XY:

127614

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.647

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.423

GnomAD4 exome

AF:

0.397

AC:

561156

AN:

1412774

Hom.:

114192

Cov.:

AF XY:

0.399

AC XY:

280425

AN XY:

702740

show subpopulations

Gnomad4 AFR exome

AF:

0.466

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.479

Gnomad4 EAS exome

AF:

0.644

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.377

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.426

AC:

64852

AN:

152132

Hom.:

14147

Cov.:

AF XY:

0.427

AC XY:

31735

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.454

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.645

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.379

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.404

Hom.:

4561

Bravo

AF:

0.440

Asia WGS

AF:

0.534

AC:

1856

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.69

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over