4-102701594-G-T

Variant names:

• chr4-102701594-G-T
• rs227292
• NM_005908.4:c.674-10823C>A

Variant summary

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

The NM_005908.4(MANBA):​c.674-10823C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 149,170 control chromosomes in the GnomAD database, including 31,053 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 0.64 (31053 hom., cov: 26)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANBA	NM_005908.4	c.674-10823C>A		intron_variant	Intron 5 of 16	ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1	c.599-10823C>A		intron_variant	Intron 6 of 17		XP_047271648.1
MANBA	XM_047415693.1	c.599-10823C>A		intron_variant	Intron 6 of 17		XP_047271649.1
MANBA	XM_047415694.1	c.26-10823C>A		intron_variant	Intron 1 of 12		XP_047271650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2	c.674-10823C>A		intron_variant	Intron 5 of 16		NM_005908.4	ENSP00000495247.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 95811 AN: 149084 Hom.: 31028 Cov.: 26

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.643 AC: 95876 AN: 149170 Hom.: 31053 Cov.: 26 AF XY: 0.644 AC XY: 46796 AN XY: 72684

African (AFR) AF: 0.586 AC: 23676 AN: 40402

American (AMR) AF: 0.614 AC: 9243 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2132 AN: 3414

East Asian (EAS) AF: 0.777 AC: 3922 AN: 5050

South Asian (SAS) AF: 0.792 AC: 3740 AN: 4722

European-Finnish (FIN) AF: 0.651 AC: 6754 AN: 10368

Middle Eastern (MID) AF: 0.598 AC: 171 AN: 286

European-Non Finnish (NFE) AF: 0.661 AC: 44255 AN: 66904

Other (OTH) AF: 0.643 AC: 1328 AN: 2064

Alfa AF: 0.634 Hom.: 3115

Bravo AF: 0.636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-2.3
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: rs227292; hg19: chr4-103622751;