rs223498

chr4-102730805-A-Cchr4-102730805-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005908.4(MANBA):c.178-4122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 425,652 control chromosomes in the GnomAD database, including 64,929 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (27812 hom., cov: 31)
  • Exomes 𝑓: 0.52 (37117 hom.)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.178-4122T>G		intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.-3367-69T>G		intron_variant
MANBA	XM_047415693.1	c.-3367-69T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.178-4122T>G		intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89108 AN: 151806 Hom.: 27763 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.516 AC: 141346 AN: 273728 Hom.: 37117 AF XY: 0.513 AC XY: 79474 AN XY: 154980

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.674

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.513

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.587 AC: 89209 AN: 151924 Hom.: 27812 Cov.: 31 AF XY: 0.587 AC XY: 43577 AN XY: 74250

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.578

Alfa AF: 0.507 Hom.: 27129

Bravo AF: 0.610

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.63

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: rs223498; hg19: chr4-103651962; COSMIC: COSV56966006; COSMIC: COSV56966006;