rs228614

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
MANBA	NM_005908.4	c.1704+202C>T		intron_variant		ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1	c.1629+202C>T		intron_variant			XP_047271648.1
MANBA	XM_047415693.1	c.1629+202C>T		intron_variant			XP_047271649.1
MANBA	XM_047415694.1	c.1056+202C>T		intron_variant			XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2	c.1704+202C>T		intron_variant			NM_005908.4	ENSP00000495247	P1

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

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.465

Alfa AF: 0.479 Hom.: 38222

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.23

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

Other links and lift over

dbSNP: rs228614; hg19: chr4-103578637;