4-6611525-T-G

Position:

• chr4-6611525-T-G

Variant summary

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

The NM_015274.3(MAN2B2):​c.2563+247T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,998 control chromosomes in the GnomAD database, including 4,949 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 0.24 (4949 hom., cov: 33)
• Consequence: MAN2B2 NM_015274.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2B2	NM_015274.3	c.2563+247T>G		intron_variant		ENST00000285599.8
MAN2B2	NM_001292038.2	c.2410+247T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2B2	ENST00000285599.8	c.2563+247T>G		intron_variant		1	NM_015274.3	P1
MAN2B2	ENST00000504248.5	c.2410+247T>G		intron_variant		2
MAN2B2	ENST00000505907.1	c.2559+247T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36754 AN: 151888 Hom.: 4922 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.242 AC: 36827 AN: 151998 Hom.: 4949 Cov.: 33 AF XY: 0.241 AC XY: 17919 AN XY: 74302

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.244

Alfa AF: 0.200 Hom.: 1467

Bravo AF: 0.257

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.82

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: rs6815746; hg19: chr4-6613252;