rs11003125

Positions:

• chr10-52772254-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-10+483C>G		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-25+483C>G		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-10+483C>G		intron_variant			NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000675947.1	c.-25+483C>G		intron_variant				ENSP00000502615	P1

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

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.319

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11003125; hg19: chr10-54532014;