rs223507

Variant names:

• chr4-102712658-G-A
• rs223507
• NM_005908.4:c.673+1780C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005908.4(MANBA):​c.673+1780C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,664 control chromosomes in the GnomAD database, including 10,301 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 0.36 (10301 hom., cov: 30)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 2 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]

MANBA Gene-Disease associations (from GenCC):

• beta-mannosidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 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.673+1780C>T		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.673+1780C>T		intron	N/A	ENSP00000495247.1
	MANBA	ENST00000642252.1		c.673+1780C>T		intron	N/A	ENSP00000495483.1
	MANBA	ENST00000644159.1		c.673+1780C>T		intron	N/A	ENSP00000494462.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55010 AN: 151548 Hom.: 10297 Cov.: 30

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.363 AC: 55039 AN: 151664 Hom.: 10301 Cov.: 30 AF XY: 0.361 AC XY: 26712 AN XY: 74062

African (AFR) AF: 0.439 AC: 18138 AN: 41318

American (AMR) AF: 0.386 AC: 5875 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3466

East Asian (EAS) AF: 0.222 AC: 1137 AN: 5132

South Asian (SAS) AF: 0.205 AC: 987 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3621 AN: 10478

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22854 AN: 67912

Other (OTH) AF: 0.360 AC: 759 AN: 2106

Alfa AF: 0.365 Hom.: 1254

Bravo AF: 0.373

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.43
PhyloP100		-0.75
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: rs223507; hg19: chr4-103633815;