4-6576760-A-G

Variant names:

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

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=-0.98).
• BP6: Variant 4-6576760-A-G is Benign according to our data. Variant chr4-6576760-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2B2	NM_015274.3	c.285+36A>G		intron_variant	Intron 2 of 18	ENST00000285599.8	NP_056089.1
MAN2B2	NM_001292038.2	c.285+36A>G		intron_variant	Intron 2 of 18		NP_001278967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2B2	ENST00000285599.8	c.285+36A>G		intron_variant	Intron 2 of 18	1	NM_015274.3	ENSP00000285599.3
MAN2B2	ENST00000504248.5	c.285+36A>G		intron_variant	Intron 2 of 18	2		ENSP00000423129.1
MAN2B2	ENST00000505907.1	c.279+36A>G		intron_variant	Intron 2 of 16	2		ENSP00000426273.1

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

GnomAD3 exomes AF: 0.839 AC: 209401 AN: 249528 Hom.: 88083 AF XY: 0.840 AC XY: 113490 AN XY: 135112

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 SAS exome AF: 0.833

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

Gnomad4 AFR exome AF: 0.754

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.868

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.836

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

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.799

Alfa AF: 0.836 Hom.: 27589

Bravo AF: 0.811

Asia WGS AF: 0.850 AC: 2956 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.41

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: rs4689485; hg19: chr4-6578487;