4-102634462-C-G

Position:

• chr4-102634462-C-G

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.2415+326G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,638 control chromosomes in the GnomAD database, including 23,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (23188 hom., cov: 32)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.535

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=-0.84).
• BP6: Variant 4-102634462-C-G is Benign according to our data. Variant chr4-102634462-C-G is described in ClinVar as [Benign]. Clinvar id is 667480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.2415+326G>C		intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.2340+326G>C		intron_variant
MANBA	XM_047415693.1	c.2340+326G>C		intron_variant
MANBA	XM_047415694.1	c.1767+326G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.2415+326G>C		intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83051 AN: 151520 Hom.: 23150 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.548 AC: 83136 AN: 151638 Hom.: 23188 Cov.: 32 AF XY: 0.547 AC XY: 40516 AN XY: 74068

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.548

Alfa AF: 0.363 Hom.: 781

Bravo AF: 0.567

Asia WGS AF: 0.505 AC: 1753 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 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.61

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: rs6813322; hg19: chr4-103555619;