rs223493

Positions:

• chr4-102747187-T-G

Variant summary

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

The NM_005908.4(MANBA):​c.177+13531A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 148,908 control chromosomes in the GnomAD database, including 6,581 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 0.29 (6581 hom., cov: 30)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.177+13531A>C		intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.-3368+13531A>C		intron_variant
MANBA	XM_047415693.1	c.-3368+13137A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.177+13531A>C		intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43164 AN: 148798 Hom.: 6576 Cov.: 30

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.290 AC: 43203 AN: 148908 Hom.: 6581 Cov.: 30 AF XY: 0.289 AC XY: 20981 AN XY: 72718

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.278

Alfa AF: 0.281 Hom.: 780

Bravo AF: 0.299

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs223493; hg19: chr4-103668344;