rs3764809

Variant names:

• chr4-6578556-A-G
• rs3764809
• NM_015274.3:c.391+58A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-6578556-A-G
• chr4-6578556-A-T

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.391+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,427,880 control chromosomes in the GnomAD database, including 82,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7563 hom., cov: 32)
  • Exomes 𝑓: 0.34 (75277 hom.)
• Consequence: MAN2B2 NM_015274.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06
• Publications: 4 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=-0.92).
• BP6: Variant 4-6578556-A-G is Benign according to our data. Variant chr4-6578556-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 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.391+58A>G		intron	N/A	NP_056089.1	Q9Y2E5-1
	MAN2B2	NM_001292038.2		c.391+58A>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.391+58A>G		intron	N/A	ENSP00000285599.3	Q9Y2E5-1
	MAN2B2	ENST00000868575.1		c.391+58A>G		intron	N/A	ENSP00000538634.1
	MAN2B2	ENST00000868574.1		c.529+58A>G		intron	N/A	ENSP00000538633.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46429 AN: 151880 Hom.: 7550 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.340 AC: 434056 AN: 1275880 Hom.: 75277 AF XY: 0.340 AC XY: 216995 AN XY: 638000

African (AFR) AF: 0.200 AC: 5850 AN: 29266

American (AMR) AF: 0.355 AC: 13737 AN: 38688

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 9469 AN: 24374

East Asian (EAS) AF: 0.529 AC: 19214 AN: 36334

South Asian (SAS) AF: 0.344 AC: 27053 AN: 78644

European-Finnish (FIN) AF: 0.304 AC: 14771 AN: 48592

Middle Eastern (MID) AF: 0.302 AC: 1622 AN: 5362

European-Non Finnish (NFE) AF: 0.337 AC: 323711 AN: 960598

Other (OTH) AF: 0.345 AC: 18629 AN: 54022

GnomAD4 genome AF: 0.306 AC: 46475 AN: 152000 Hom.: 7563 Cov.: 32 AF XY: 0.303 AC XY: 22497 AN XY: 74304

African (AFR) AF: 0.201 AC: 8323 AN: 41472

American (AMR) AF: 0.324 AC: 4948 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2691 AN: 5152

South Asian (SAS) AF: 0.354 AC: 1711 AN: 4828

European-Finnish (FIN) AF: 0.315 AC: 3322 AN: 10560

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23143 AN: 67928

Other (OTH) AF: 0.300 AC: 632 AN: 2106

Alfa AF: 0.322 Hom.: 1038

Bravo AF: 0.303

Asia WGS AF: 0.374 AC: 1303 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	-0.92
CADD	Benign	0.063
DANN	Benign	0.51
PhyloP100		-2.1
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: rs3764809; hg19: chr4-6580283;