dbSNP rs930509: MBL2:c.374-83G>C (chr10-52768593-C-G) – 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.374-83G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,005,892 control chromosomes in the GnomAD database, including 326,851 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 0.84 ( 53499 hom., cov: 33)

Exomes 𝑓: 0.80 ( 273352 hom. )

Consequence

MBL2
NM_001378373.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793

Publications

15 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:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1 link	c.374-83G>C	intron_variant	Intron 4 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3 link	c.374-83G>C	intron_variant	Intron 3 of 3		NP_000233.1	P11226
MBL2	NM_001378374.1 link	c.374-83G>C	intron_variant	Intron 4 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBL2	ENST00000674931.1 link	c.374-83G>C	intron_variant	Intron 4 of 4		NM_001378373.1	ENSP00000502789.1	P11226
MBL2	ENST00000373968.3 link	c.374-83G>C	intron_variant	Intron 3 of 3	1		ENSP00000363079.3	P11226
MBL2	ENST00000675947.1 link	c.374-83G>C	intron_variant	Intron 4 of 4			ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127201

AN:

151868

Hom.:

53444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.881

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.791

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.823

GnomAD4 exome

AF:

0.799

AC:

682290

AN:

853906

Hom.:

273352

AF XY:

0.798

AC XY:

343790

AN XY:

431000

show subpopulations

African (AFR)

AF:

0.877

AC:

18604

AN:

21214

American (AMR)

AF:

0.903

AC:

20403

AN:

22598

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

13443

AN:

15774

East Asian (EAS)

AF:

0.869

AC:

30277

AN:

34830

South Asian (SAS)

AF:

0.742

AC:

36085

AN:

48632

European-Finnish (FIN)

AF:

0.793

AC:

30071

AN:

37926

Middle Eastern (MID)

AF:

0.743

AC:

3145

AN:

4232

European-Non Finnish (NFE)

AF:

0.792

AC:

498710

AN:

629678

Other (OTH)

AF:

0.809

AC:

31552

AN:

39022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

6134

12268

18402

24536

30670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10026

20052

30078

40104

50130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.838

AC:

127316

AN:

151986

Hom.:

53499

Cov.:

AF XY:

0.838

AC XY:

62229

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.883

AC:

36533

AN:

41358

American (AMR)

AF:

0.881

AC:

13448

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

2958

AN:

3464

East Asian (EAS)

AF:

0.842

AC:

4354

AN:

5170

South Asian (SAS)

AF:

0.751

AC:

3619

AN:

4820

European-Finnish (FIN)

AF:

0.791

AC:

8380

AN:

10592

Middle Eastern (MID)

AF:

0.788

AC:

230

AN:

292

European-Non Finnish (NFE)

AF:

0.812

AC:

55200

AN:

68010

Other (OTH)

AF:

0.825

AC:

1738

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1064

2128

3192

4256

5320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.748

Hom.:

2162

Bravo

AF:

0.851

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.0

(source)

DANN

Benign

0.68

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over