4-102632290-GAA-GA

Variant names:

• chr4-102632290-GA-G
• rs5860729
• NM_005908.4:c.2416-10delT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005908.4(MANBA):​c.2416-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (23011 hom., cov: 0)
  • Exomes 𝑓: 0.52 (140227 hom.)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.178

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 -16 ACMG points.

• BP6: Variant 4-102632290-GA-G is Benign according to our data. Variant chr4-102632290-GA-G is described in ClinVar as [Benign]. Clinvar id is 403070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-102632290-GA-G is described in Lovd as [Benign]. Variant chr4-102632290-GA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANBA	NM_005908.4	c.2416-10delT		intron_variant	Intron 16 of 16	ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1	c.2341-10delT		intron_variant	Intron 17 of 17		XP_047271648.1
MANBA	XM_047415693.1	c.2341-10delT		intron_variant	Intron 17 of 17		XP_047271649.1
MANBA	XM_047415694.1	c.1768-10delT		intron_variant	Intron 12 of 12		XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2	c.2416-10delT		intron_variant	Intron 16 of 16		NM_005908.4	ENSP00000495247.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 82581 AN: 148198 Hom.: 22977 Cov.: 0

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.565

GnomAD3 exomes AF: 0.598 AC: 122664 AN: 205224 Hom.: 30759 AF XY: 0.590 AC XY: 65503 AN XY: 111060

Gnomad AFR exome AF: 0.666

Gnomad AMR exome AF: 0.736

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.585

Gnomad SAS exome AF: 0.533

Gnomad FIN exome AF: 0.555

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.521 AC: 630786 AN: 1210052 Hom.: 140227 Cov.: 0 AF XY: 0.521 AC XY: 315924 AN XY: 606580

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.557 AC: 82661 AN: 148304 Hom.: 23011 Cov.: 0 AF XY: 0.557 AC XY: 40212 AN XY: 72224

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.560

Bravo AF: 0.561

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Beta-D-mannosidosis Benign:3

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Latino/Admixed American population allele frequency is 72.75% (rs200835097, 22,987/31,314 alleles, 7,883 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.1.0, this variant is classified as BENIGN. Following criteria are met: BA1 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Mar 21, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Mar 16, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs5860729; hg19: chr4-103553447;