dbSNP rs11595876: MBL2:c.*1135A>G (chr10-52767002-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378373.1(MBL2):c.*1135A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 152,020 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.046 ( 226 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MBL2
NM_001378373.1 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.853

Publications

10 publications found

Variant links:

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]

MBL2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0668 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBL2	NM_001378373.1	MANE Select	c.*1135A>G	3_prime_UTR	Exon 5 of 5	NP_001365302.1	P11226
MBL2	NM_000242.3		c.*1135A>G	3_prime_UTR	Exon 4 of 4	NP_000233.1	P11226
MBL2	NM_001378374.1		c.*1135A>G	3_prime_UTR	Exon 5 of 5	NP_001365303.1	P11226

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBL2	ENST00000674931.1	MANE Select	c.*1135A>G	3_prime_UTR	Exon 5 of 5	ENSP00000502789.1	P11226
MBL2	ENST00000373968.3	TSL:1	c.*1135A>G	3_prime_UTR	Exon 4 of 4	ENSP00000363079.3	P11226
MBL2	ENST00000675947.1		c.*1135A>G	3_prime_UTR	Exon 5 of 5	ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes

AF:

0.0462

AC:

7019

AN:

151902

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0417

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0684

Gnomad OTH

AF:

0.0445

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0461

AC:

7015

AN:

152020

Hom.:

226

Cov.:

AF XY:

0.0442

AC XY:

3285

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0152

AC:

630

AN:

41404

American (AMR)

AF:

0.0415

AC:

634

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

348

AN:

3456

East Asian (EAS)

AF:

0.000581

AC:

AN:

5166

South Asian (SAS)

AF:

0.0189

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0462

AC:

490

AN:

10602

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0684

AC:

4650

AN:

67990

Other (OTH)

AF:

0.0435

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

354

708

1062

1416

1770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0607

Hom.:

507

Bravo

AF:

0.0447

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mannose-binding lectin deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.25

(source)

DANN

Benign

0.45

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over