chr4-102632290-GA-G

Variant names:

• chr4-102632290-GA-G
• rs5860729
• NM_005908.4:c.2416-10delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005908.4(MANBA):​c.2416-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (23011 hom., cov: 0)
  • Exomes 𝑓: 0.52 (140227 hom.)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.178
• Publications: 3 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: Ambry Genetics, Orphanet, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 4-102632290-GA-G is Benign according to our data. Variant chr4-102632290-GA-G is described in ClinVar as Benign. ClinVar VariationId is 403070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	NM_005908.4	MANE Select	c.2416-10delT		intron	N/A	NP_005899.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBA	ENST00000647097.2	MANE Select	c.2416-10delT		intron	N/A	ENSP00000495247.1	O00462
	MANBA	ENST00000642252.1		c.2554-10delT		intron	N/A	ENSP00000495483.1	A0A2R8YEC9
	MANBA	ENST00000954426.1		c.2515-10delT		intron	N/A	ENSP00000624485.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 82581 AN: 148198 Hom.: 22977 Cov.: 0

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.565

GnomAD2 exomes AF: 0.598 AC: 122664 AN: 205224 AF XY: 0.590

Gnomad AFR exome AF: 0.666

Gnomad AMR exome AF: 0.736

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.585

Gnomad FIN exome AF: 0.555

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.521 AC: 630786 AN: 1210052 Hom.: 140227 Cov.: 0 AF XY: 0.521 AC XY: 315924 AN XY: 606580

African (AFR) AF: 0.616 AC: 17277 AN: 28030

American (AMR) AF: 0.714 AC: 29276 AN: 40992

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 11696 AN: 22392

East Asian (EAS) AF: 0.533 AC: 18179 AN: 34128

South Asian (SAS) AF: 0.495 AC: 36601 AN: 73982

European-Finnish (FIN) AF: 0.517 AC: 24048 AN: 46504

Middle Eastern (MID) AF: 0.579 AC: 2962 AN: 5120

European-Non Finnish (NFE) AF: 0.510 AC: 463532 AN: 908294

Other (OTH) AF: 0.538 AC: 27215 AN: 50610

GnomAD4 genome AF: 0.557 AC: 82661 AN: 148304 Hom.: 23011 Cov.: 0 AF XY: 0.557 AC XY: 40212 AN XY: 72224

African (AFR) AF: 0.634 AC: 25783 AN: 40672

American (AMR) AF: 0.621 AC: 9310 AN: 15002

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1761 AN: 3416

East Asian (EAS) AF: 0.525 AC: 2637 AN: 5026

South Asian (SAS) AF: 0.461 AC: 2149 AN: 4660

European-Finnish (FIN) AF: 0.496 AC: 4812 AN: 9708

Middle Eastern (MID) AF: 0.614 AC: 178 AN: 290

European-Non Finnish (NFE) AF: 0.516 AC: 34365 AN: 66588

Other (OTH) AF: 0.560 AC: 1145 AN: 2044

Alfa AF: 0.434 Hom.: 1436

Bravo AF: 0.561

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Beta-D-mannosidosis (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
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: rs5860729; hg19: chr4-103553447;