rs223498

Variant names:

• chr4-102730805-A-C
• rs223498
• NM_005908.4:c.178-4122T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-102730805-A-C
• chr4-102730805-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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]

LRRC37A15P (HGNC:43819): (leucine rich repeat containing 37 member A15, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	NM_005908.4	MANE Select	c.178-4122T>G		intron	N/A	NP_005899.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	ENST00000647097.2	MANE Select	c.178-4122T>G		intron	N/A	ENSP00000495247.1
	MANBA	ENST00000642252.1		c.178-4122T>G		intron	N/A	ENSP00000495483.1
	MANBA	ENST00000954426.1		c.178-4122T>G		intron	N/A	ENSP00000624485.1

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

African (AFR) AF: 0.809 AC: 5811 AN: 7184

American (AMR) AF: 0.674 AC: 13896 AN: 20632

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 2814 AN: 5536

East Asian (EAS) AF: 0.513 AC: 6312 AN: 12296

South Asian (SAS) AF: 0.496 AC: 24718 AN: 49854

European-Finnish (FIN) AF: 0.464 AC: 6441 AN: 13870

Middle Eastern (MID) AF: 0.580 AC: 1367 AN: 2358

European-Non Finnish (NFE) AF: 0.491 AC: 73343 AN: 149414

Other (OTH) AF: 0.528 AC: 6644 AN: 12584

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

African (AFR) AF: 0.806 AC: 33406 AN: 41448

American (AMR) AF: 0.618 AC: 9435 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1746 AN: 3464

East Asian (EAS) AF: 0.519 AC: 2682 AN: 5166

South Asian (SAS) AF: 0.484 AC: 2329 AN: 4812

European-Finnish (FIN) AF: 0.468 AC: 4935 AN: 10554

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32783 AN: 67906

Other (OTH) AF: 0.578 AC: 1218 AN: 2106

Alfa AF: 0.517 Hom.: 38137

Bravo AF: 0.610

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.94
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: rs223498; hg19: chr4-103651962; COSMIC: COSV56966006; COSMIC: COSV56966006;