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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005908.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	NM_005908.4	MANE Select	c.1704+202C>T		intron	N/A	NP_005899.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	ENST00000647097.2	MANE Select	c.1704+202C>T		intron	N/A	ENSP00000495247.1	O00462
	MANBA	ENST00000642252.1		c.1842+202C>T		intron	N/A	ENSP00000495483.1	A0A2R8YEC9
	MANBA	ENST00000954426.1		c.1803+202C>T		intron	N/A	ENSP00000624485.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;