rs11003123

Positions:

• chr10-52771774-G-A

Variant summary

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

The NM_001378373.1(MBL2):​c.-9-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,332,208 control chromosomes in the GnomAD database, including 38,605 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 0.29 (7902 hom., cov: 32)
  • Exomes 𝑓: 0.22 (30703 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-130C>T		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-115C>T		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-130C>T		intron_variant			NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000675947.1	c.-24-115C>T		intron_variant				ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44495 AN: 151964 Hom.: 7889 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.221 AC: 261155 AN: 1180126 Hom.: 30703 AF XY: 0.222 AC XY: 127578 AN XY: 575680

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.293 AC: 44541 AN: 152082 Hom.: 7902 Cov.: 32 AF XY: 0.288 AC XY: 21420 AN XY: 74336

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.266

Alfa AF: 0.234 Hom.: 7211

Bravo AF: 0.303

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11003123; hg19: chr10-54531534;