4-6578556-A-G

Position:

• chr4-6578556-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2B2	NM_015274.3	c.391+58A>G		intron_variant		ENST00000285599.8
MAN2B2	NM_001292038.2	c.391+58A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2B2	ENST00000285599.8	c.391+58A>G		intron_variant		1	NM_015274.3	P1
MAN2B2	ENST00000504248.5	c.391+58A>G		intron_variant		2
MAN2B2	ENST00000505907.1	c.387+58A>G		intron_variant		2

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.345

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

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.300

Alfa AF: 0.322 Hom.: 1038

Bravo AF: 0.303

Asia WGS AF: 0.374 AC: 1303 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 62% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.063
DANN	Benign	0.51

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: rs3764809; hg19: chr4-6580283;