chr4-102712658-G-A

Position:

• chr4-102712658-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.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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANBA	NM_005908.4	c.673+1780C>T		intron_variant		ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1	c.598+1780C>T		intron_variant			XP_047271648.1
MANBA	XM_047415693.1	c.598+1780C>T		intron_variant			XP_047271649.1
MANBA	XM_047415694.1	c.25+10213C>T		intron_variant			XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2	c.673+1780C>T		intron_variant			NM_005908.4	ENSP00000495247.1

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

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.360

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.43

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: rs223507; hg19: chr4-103633815;