Variant 4-102631673-G-A 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_005908.4(MANBA):c.*384C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 470,540 control chromosomes in the GnomAD database, including 66,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23357 hom., cov: 31)

Exomes 𝑓: 0.51 ( 42803 hom. )

Consequence

MANBA
NM_005908.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.118

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 4-102631673-G-A is Benign according to our data. Variant chr4-102631673-G-A is described in ClinVar as [Benign]. Clinvar id is 347068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MANBA	NM_005908.4 linkuse as main transcript	c.*384C>T	3_prime_UTR_variant	17/17	ENST00000647097.2
MANBA	XM_047415692.1 linkuse as main transcript	c.*384C>T	3_prime_UTR_variant	18/18
MANBA	XM_047415693.1 linkuse as main transcript	c.*384C>T	3_prime_UTR_variant	18/18
MANBA	XM_047415694.1 linkuse as main transcript	c.*384C>T	3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2 linkuse as main transcript	c.*384C>T		3_prime_UTR_variant	17/17		NM_005908.4	P1

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83374

AN:

151640

Hom.:

23320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.518

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.513

AC:

163620

AN:

318782

Hom.:

42803

Cov.:

AF XY:

0.512

AC XY:

83033

AN XY:

162304

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.677

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.510

Gnomad4 OTH exome

AF:

0.538

GnomAD4 genome

AF:

0.550

AC:

83458

AN:

151758

Hom.:

23357

Cov.:

AF XY:

0.549

AC XY:

40687

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.632

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.519

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.549

Alfa

AF:

0.538

Hom.:

8636

Bravo

AF:

0.567

Asia WGS

AF:

0.506

AC:

1754

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Beta-D-mannosidosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

-0.95

CADD

Benign

1.1

DANN

Benign

0.76

Splicing

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