rs228614

Variant names:

• chr4-102657480-G-A
• rs228614
• NM_005908.4:c.1704+202C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-102657480-G-A
• chr4-102657480-G-C
• chr4-102657480-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005908.4(MANBA):​c.1704+202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,900 control chromosomes in the GnomAD database, including 19,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19018 hom., cov: 31)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0620
• Publications: 61 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 4-102657480-G-A is Benign according to our data. Variant chr4-102657480-G-A is described in ClinVar as Benign. ClinVar VariationId is 1261822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANBA	NM_005908.4	c.1704+202C>T		intron_variant	Intron 12 of 16	ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1	c.1629+202C>T		intron_variant	Intron 13 of 17		XP_047271648.1
MANBA	XM_047415693.1	c.1629+202C>T		intron_variant	Intron 13 of 17		XP_047271649.1
MANBA	XM_047415694.1	c.1056+202C>T		intron_variant	Intron 8 of 12		XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2	c.1704+202C>T		intron_variant	Intron 12 of 16		NM_005908.4	ENSP00000495247.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75423 AN: 151782 Hom.: 18975 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.459

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75517 AN: 151900 Hom.: 19018 Cov.: 31 AF XY: 0.497 AC XY: 36913 AN XY: 74244

African (AFR) AF: 0.555 AC: 23004 AN: 41424

American (AMR) AF: 0.393 AC: 6000 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2662 AN: 5160

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4816

European-Finnish (FIN) AF: 0.516 AC: 5433 AN: 10520

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32751 AN: 67946

Other (OTH) AF: 0.465 AC: 981 AN: 2108

Alfa AF: 0.481 Hom.: 61211

Bravo AF: 0.486

Asia WGS AF: 0.520 AC: 1812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.23
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs228614; hg19: chr4-103578637;