10-52771925-G-C

Variant names:

• chr10-52771925-G-C
• rs7096206
• NM_001378373.1:c.-9-281C>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.-9-281C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,126 control chromosomes in the GnomAD database, including 50,206 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 0.81 (50206 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 201 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.-9-281C>G		intron	N/A	NP_001365302.1
	MBL2	NM_001378374.1		c.-24-266C>G		intron	N/A	NP_001365303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.-9-281C>G		intron	N/A	ENSP00000502789.1
	MBL2	ENST00000675947.1		c.-24-266C>G		intron	N/A	ENSP00000502615.1
	MBL2	ENST00000373968.3	TSL:1	c.-290C>G		upstream_gene	N/A	ENSP00000363079.3

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123347 AN: 152008 Hom.: 50149 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.812 AC: 123464 AN: 152126 Hom.: 50206 Cov.: 32 AF XY: 0.814 AC XY: 60556 AN XY: 74368

African (AFR) AF: 0.851 AC: 35341 AN: 41514

American (AMR) AF: 0.868 AC: 13277 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2932 AN: 3462

East Asian (EAS) AF: 0.836 AC: 4301 AN: 5146

South Asian (SAS) AF: 0.742 AC: 3572 AN: 4816

European-Finnish (FIN) AF: 0.795 AC: 8420 AN: 10594

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52843 AN: 67988

Other (OTH) AF: 0.806 AC: 1695 AN: 2104

Alfa AF: 0.711 Hom.: 2029

Bravo AF: 0.823

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.48
PhyloP100		-0.83
PromoterAI		-0.0096	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7096206; hg19: chr10-54531685;