rs228611

Positions:

• chr4-102640552-G-A

Variant summary

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

The NM_005908.4(MANBA):​c.1870-695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,894 control chromosomes in the GnomAD database, including 13,361 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 0.40 (13361 hom., cov: 31)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.1870-695C>T		intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.1795-695C>T		intron_variant
MANBA	XM_047415693.1	c.1795-695C>T		intron_variant
MANBA	XM_047415694.1	c.1222-695C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.1870-695C>T		intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61372 AN: 151778 Hom.: 13350 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.404 AC: 61403 AN: 151894 Hom.: 13361 Cov.: 31 AF XY: 0.407 AC XY: 30180 AN XY: 74222

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.405

Alfa AF: 0.457 Hom.: 7559

Bravo AF: 0.381

Asia WGS AF: 0.485 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.82

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: rs228611; hg19: chr4-103561709;