chr10-52772254-G-C

Variant names:

• chr10-52772254-G-C
• rs11003125
• NM_001378373.1:c.-10+483C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378373.1(MBL2):​c.-10+483C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,034 control chromosomes in the GnomAD database, including 8,586 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 0.31 (8586 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 135 publications found

Genes affected

MBL2 (HGNC:6922): (mannose binding lectin 2) This gene encodes the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. [provided by RefSeq, Jun 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378373.1. 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
	MBL2	NM_001378373.1	MANE Select	c.-10+483C>G		intron	N/A	NP_001365302.1	P11226
	MBL2	NM_001378374.1		c.-25+483C>G		intron	N/A	NP_001365303.1	P11226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.-10+483C>G		intron	N/A	ENSP00000502789.1	P11226
	MBL2	ENST00000675947.1		c.-25+483C>G		intron	N/A	ENSP00000502615.1	P11226
	MBL2	ENST00000877442.1		c.-10+469C>G		intron	N/A	ENSP00000547501.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47763 AN: 151916 Hom.: 8577 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.314 AC: 47784 AN: 152034 Hom.: 8586 Cov.: 32 AF XY: 0.319 AC XY: 23724 AN XY: 74324

African (AFR) AF: 0.130 AC: 5387 AN: 41502

American (AMR) AF: 0.407 AC: 6226 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3462

East Asian (EAS) AF: 0.467 AC: 2397 AN: 5130

South Asian (SAS) AF: 0.350 AC: 1685 AN: 4816

European-Finnish (FIN) AF: 0.404 AC: 4274 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25270 AN: 67954

Other (OTH) AF: 0.319 AC: 672 AN: 2108

Alfa AF: 0.341 Hom.: 1173

Bravo AF: 0.311

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		-0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11003125; hg19: chr10-54532014;