rs4689485

Variant names:

• chr4-6576760-A-G
• rs4689485
• NM_015274.3:c.285+36A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015274.3(MAN2B2):​c.285+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,607,672 control chromosomes in the GnomAD database, including 559,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (50862 hom., cov: 33)
  • Exomes 𝑓: 0.84 (508197 hom.)
• Consequence: MAN2B2 NM_015274.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28
• Publications: 10 publications found

Genes affected

MAN2B2 (HGNC:29623): (mannosidase alpha class 2B member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in mannose metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN2B2 Gene-Disease associations (from GenCC):

• MAN2B2 deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 4-6576760-A-G is Benign according to our data. Variant chr4-6576760-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015274.3. 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
	MAN2B2	NM_015274.3	MANE Select	c.285+36A>G		intron	N/A	NP_056089.1	Q9Y2E5-1
	MAN2B2	NM_001292038.2		c.285+36A>G		intron	N/A	NP_001278967.1	E9PCD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN2B2	ENST00000285599.8	TSL:1 MANE Select	c.285+36A>G		intron	N/A	ENSP00000285599.3	Q9Y2E5-1
	MAN2B2	ENST00000868575.1		c.285+36A>G		intron	N/A	ENSP00000538634.1
	MAN2B2	ENST00000868574.1		c.423+36A>G		intron	N/A	ENSP00000538633.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124056 AN: 152016 Hom.: 50815 Cov.: 33

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.796

GnomAD2 exomes AF: 0.839 AC: 209401 AN: 249528 AF XY: 0.840

Gnomad AFR exome AF: 0.748

Gnomad AMR exome AF: 0.868

Gnomad ASJ exome AF: 0.870

Gnomad EAS exome AF: 0.859

Gnomad FIN exome AF: 0.867

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.833

GnomAD4 exome AF: 0.835 AC: 1215564 AN: 1455538 Hom.: 508197 Cov.: 38 AF XY: 0.835 AC XY: 603732 AN XY: 722914

African (AFR) AF: 0.754 AC: 25161 AN: 33384

American (AMR) AF: 0.864 AC: 38580 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 22824 AN: 26088

East Asian (EAS) AF: 0.851 AC: 33630 AN: 39506

South Asian (SAS) AF: 0.835 AC: 71884 AN: 86128

European-Finnish (FIN) AF: 0.868 AC: 45822 AN: 52798

Middle Eastern (MID) AF: 0.833 AC: 4789 AN: 5746

European-Non Finnish (NFE) AF: 0.833 AC: 922592 AN: 1107110

Other (OTH) AF: 0.836 AC: 50282 AN: 60142

GnomAD4 genome AF: 0.816 AC: 124163 AN: 152134 Hom.: 50862 Cov.: 33 AF XY: 0.816 AC XY: 60652 AN XY: 74358

African (AFR) AF: 0.749 AC: 31069 AN: 41496

American (AMR) AF: 0.820 AC: 12538 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3030 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4396 AN: 5132

South Asian (SAS) AF: 0.839 AC: 4049 AN: 4824

European-Finnish (FIN) AF: 0.873 AC: 9262 AN: 10614

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57090 AN: 67984

Other (OTH) AF: 0.799 AC: 1685 AN: 2110

Alfa AF: 0.835 Hom.: 30515

Bravo AF: 0.811

Asia WGS AF: 0.850 AC: 2956 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-1.3
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: rs4689485; hg19: chr4-6578487;