chr4-102719745-C-T

Position:

• chr4-102719745-C-T

Variant summary

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

The NM_005908.4(MANBA):​c.549+3126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,274 control chromosomes in the GnomAD database, including 747 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 0.058 (747 hom., cov: 32)
• Consequence: MANBA NM_005908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANBA	NM_005908.4	c.549+3126G>A		intron_variant		ENST00000647097.2
MANBA	XM_047415692.1	c.474+3126G>A		intron_variant
MANBA	XM_047415693.1	c.474+3126G>A		intron_variant
MANBA	XM_047415694.1	c.25+3126G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANBA	ENST00000647097.2	c.549+3126G>A		intron_variant			NM_005908.4	P1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8786 AN: 152158 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00756

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0579 AC: 8814 AN: 152274 Hom.: 747 Cov.: 32 AF XY: 0.0564 AC XY: 4197 AN XY: 74468

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00756

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0377 Hom.: 64

Bravo AF: 0.0663

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.42

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: rs10489108; hg19: chr4-103640902;